New comprehensive biochemistry vol 25 protein lipid interactions

Elsevier Science Publishers B.V PO Box 211 1000 AE Amsterdam The Netherlands Library of Congress Cataloging-in-Publication Data Protein-lipid interactions I editor, A Watts p cm (New comprehensive biochemistry ; v 25) Includes bibliographical references and index ISBN 0-444-81575-9 (alk paper) ISBN 0-444-80303-3 (series) Membrane proteins Membrane lipids Lipoproteins I Watts, A II Series Protein binding [DNLM: Membrane Proteins metabolism Membrane Lipids-metabolism Cell Membrane metabolism W1 NE372F v 25 1993 / QU 55 P96655 19931 QD415.N48 vol 25 574.19'2 s dc20 [574.19'245] DNLMlDLC for Library of Congress 93-1825 CIP ISBN 444 81575 ISBN 444 80303 (series) 01993 Elsevier Science Publishers B.V All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher, Elsevier Science Publishers B.V, Copyright and Permissions Department, PO Box 521, 1000 AM Amsterdam, the Netherlands No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of the rapid advances in the medical sciences, the publisher recommends that independent verification of diagnoses and drug dosages should be made Special regulationsfor readers in the USA - This publication has been registered with the Copyright Clearance Center Inc (CCC), Salem, Massachusetts Information can be obtained from the CCC about conditions under which photocopies of parts of this publication may be made in the USA All other copyright questions, including photocopying outside the USA, should be referred to the publisher Printed on acid-free paper Printed in the Netherlands Protein-Lipid Interactions Editor A Watts Department of Biochemistry, University of Oxford, Oxford, OX1 3QU United Kingdom 1993 ELSEVIER Amsterdam London New York Tokyo New Comprehensive Biochemistry Volume 25 General Editors A NEUBERGER London L.L.M van DEENEN Utrecht ELSEVIER Amsterdam London New York Tokyo vii List of contributors Jos6 Luis R Arrondo, Department of Biochemistry, University of the Basque Country, PO Box 644, 48080 Bilbao, Spain VA Bankaitis, Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, U S A F.J Barrantes, Instituto de Investigaciones Bioquimicas de Bahia Blanca, 8000 Bahia Blanca, Argentina Rodney L Biltonen, Department of Biochemistry, University of Virginia, Charlottesville, VA 22908, USA J Boulter, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU UK Rudolfo R Brenner, Instituto de Investigaciones Bioquimicas de La Plata (INIBIOLP), UNLPCONICET Facultad de Ciencias Medicas, 60 y 120, (1900), La Plata, Argentina Celina E Castuma, Instituto de Investigaciones Bioquimicas de La Plata (INIBIOLP), UNLPCONICEI: Facultad de Ciencias Medicas, 60 y 120, (1900), La Plata, Argentina Lauraine A Dalton, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, U S.A J de Gier, Department of Biochemistry of Membranes, Centrefor Biomembranes and Lipid Enzymology, University of Utrecht, Utrecht, The Netherlands A.I.P.M de Kroon, Department of Biochemistry of Membranes, Centrefor Biomembranes and Lipid Enzymology, University of Utrecht, Utrecht, The Netherlands B de Kruijff, Department of Biochemistry of Membranes, Centrefor Biomembranes and Lipid Enzymology, and Institute of Molecular Biology and Medical Biotechnology, University of Utrecht, Utrecht, The Netherlands Vlll T.M Duncan, Department of Biochemistry and Molecular Biology, SUNY Health Science Centel; Syracuse, NY 13210, U S A J Malcolm East, Department of Biochemistiy, University of Southampton, Bassett Crescent East, Southampton, SO9 3TU, U K S Fleischer, Department of Molecular Biology, Vanderbilt University, Nashville, TN 7235, USA M.K.Y Fung, Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, U S A Filix M Gohi, Department of Biochemistiy, University of the Basque Countiy, PO Box 644, 48080 Bilbao, Spain Marcus A Hemminga, Department of Molecular Physics, Agricultural University, PO Box 8128, 6700 ET Wageningen, The Netherlands M Teresa Lamy-Freund, Institute of Physics, Universidade de S Paulo, C.P 2051 6, CEP 01498, S Paulo, Brazil Anthony G Lee, Department of Biochemistry, University of Southampton, Bassett Crescent East, Southampton, SO9 3TU U K James E Mahaney, Department of Biochemistiy, University of Minnesota Medical School, Minneapolis, MN 55455, U S A Derek Marsh, Max-Planck-Institut fur biophysikalische Chemie, Abteilung Spektroskopie, Postfach 2841, WD-3400 Gottingen, Fed Rep Germany T.P McGee, Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, U S A J.O McIntyre, Department of Molecular Biology, Vanderbilt University, Nashville, TN 7235, USA Keith W Miller, Department of Biological Chemistry and Molecular Pharmacologj Haward Medical School, Boston, MA 02115, US.A ix Ole G Mouritsen, Department of Physical Chemistry, The Technical University of Denmark, Building 206, DK-2800 Lyngby, Denmark Douglas E Raines, Department of Biological Chemistry and Molecular Pharmacology, Haward Medical School, Boston, MA 02115, U S A Saffron E Rankin, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, US.A M Sami, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU UK H Sandermann Jr., GSF-Forschungszentrum fur Umwelt und Gesundheit, GmbH, Institut f u r Biochemische PJEanzenpathologie,0-8042 Neuherberg, FRG Johan C Sanders, Department of Molecular Physics, Agricultural University, PO Box 8128, 6700 ET Wageningen, The Netherlands Mantripragada B Sankaram, Department of Biochemistry, University qf Vivginia Health Sciences Center; Charlottesville, YA 22908, U S A Shirley Schreier, Department of Biochemistry, Institute of Chemistry, Universidade de S Paulo, C.P 20780, CEP 01498, S Paulo, Brazil Ruud B Spruijt, Department of Molecular Physics, Agricultural University, PO Box 8128, 6700 ET Wageningen, The Netherlands B Sternberg, Abt fur Elektronenmikroskopie, Friedrich-Schiller-Universitat Jena, Ziegelmiihlenweg I , 0-6900 Jena I , Germany David D Thomas, Department of Biochemistry, University of Minnesota Medical School, Minneapolis, MN 55455, US.A C Vinien-bryan, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU UK A Watts, Department of Biochemistry, University o j Oxford, South Parks Road, Oxford, OX1 3QU UK X C Whiteway, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK Cor J.A.M Wolfs, Department of Molecular Physics, Agricultural University, PO Box 8128, 6700 ET Wageningen, The Netherlands V Preface Protein-lipid interactions as a field of study is now a mature area, and has been reviewed in volumes and single review articles several times in the past decade or so Over this period there has not been complete agreement in the interpretation of results from a range of methods and systems Some rationalization has now been achieved and to some degree a level of consensus of opinion and description of the protein-lipid interface (as presented by Mouritsen and Biltonen from a thermodynamic viewpoint, and from a spectroscopic and structural aspect by Marsh) and its all-important relevance to the fbnctional integrity (as described by Sandermann, Duncan, McIntyre and Fleischer) of the system, has been described It was thought appropriate that a reflective view could now be presented in a volume with two objectives in mind Firstly, to look towards the future, and try to envisage how the subject may develop in the near to medium-term future Secondly, to present contrasting or complementary views on the same system, for example, the acetylcholine receptor is discussed from a predominantly structural aspect by Barrantes and from the kinetic standpoint by Rankin, Raines, Dalton and Miller Similarly, the (Ca2+-Mg2')-ATPase is considered in the sarcoplasmic reticulum by Thomas and Mahaney, and in reconstituted systems by Lee and East Recent new information has been gained about the genetic modulation of membranes and the effect on protein-lipid interactions (as discussed by McGee, Fung and Bankaitis), as well as how proteins and peptide insertion into the membrane could involve the membrane lipids (from de Kroon, de Gier and de Kruijff) An intriguing possibility that M13 bacteriophage infection can involve lipid-protein interactions is discussed by Hemminga, Sanders, Wolfs and Spruijt, where reconstitution and in vivo studies of the coat protein (a 50-mer) give information about assembly and association of the protein in the membrane Peripheral protein-lipid interactions are considered by Sankaram and Marsh, and the effects of cholesterol on lipid-protein interactions in natural membranes are considered by Castuma, Lamy-Freund, Brenner and Schreier The future possibilities for the use of FT-IR spectroscopy are considered by Arrondo and Goiii and, again looking well into the future, the way in which lipid-protein interactions may control 2D array and 3D crystal formation of integral membrane proteins is discussed by Watts, Vknien-Bryan, Sami, Whiteway, Boulter and Sternberg v1 It is hoped that this volume not only gives an update on specific aspects of the field, but also shows a way in which the phenomenon of proteinlipid interactions is now seemingly infiltrating many areas of biomembrane research, from recombinant DNA studies, protein insertion and assembly and reconstitution considerations to structural studies of membrane proteins A Watts December, 1992 A Watts (Ed.), Protein-Lipid Interactions 1993 Elsevier Science Publishers B.V All rights reserved CHAPTER Protein-lipid interactions and membrane heterogeneity Ole G MOURITSEN'>* and Rodney L BILTONEN2 'Department of Physical Chemistv, The Technical University of Denmark, Building 206, DK-2800 Lyngby, Denmark, 2Department of Biochemistry, University of nrginia, Charlottesville, VA 22908, W A Abbreviations AC DS DSC DMPC DPPC DSPC LUV alternating current distearoyl differential scanning calorimetry dimyristoyl phosphatidylcholine dipalmitoyl phosphatidylcholine distearoyl phosphatidylcholine large unilamellar vesicles MLV NMR PA PC PE PS SUV multilamellar vesicles nuclear magnetic resonance phosphatidic acid phosphatidylcholine phosphatidylethanolamine phosphatidylserine small unilarnellar vesicles Perspectives and overview 1.1 Lipids, proteins, and the biological membrane The conventional picture of the biological membrane is that of Singer and Nicolson [ 1,2] who suggested viewing the biological membrane as a fluid mosaic bimolecular lipid layer in which the various membrane components, such as proteins, enzymes, and polypeptides, are embedded or attached to The crucial property of this molecular assembly is the bilayer fluidity which assures sufficient lateral mobility of the membrane components to support biological function A fuller picture of the biological membrane considers the fluid bilayer as only part of a composite structure, see Fig 1, consisting, in the case of eucaryotic cells, of a glycocalyx structure on the outside and of a cytoskeletal scaffolding of proteins on the inside The particular engineering of this composite and its various parts has imparted the biological membrane with unique physical properties [ ] The * Associate Fellow of The Canadian Institute of Advanced Research 365 Fig Photographs show the effect of additives and pH on the morphology of bacteriorhodopsin crystals obtained by vapour diffusion (left) Needle shaped crystals (400 pm x 40 pm) in the presence of 0.18% w/v CloEg, 0.5 M sodium phosphate, pH 5.6; (right) square shaped crystals (4 pm across) obtained in 0.45M NaCI, 50mM sodium borate buffer, pH9.5, or in the presence of DPhPGF! Typically p1 drops of protein solution (15 mgiml) in 0.5% (wiv) octyl glucoside containing 3% (w/v) benzamidine, 3% (wiv) DL pipecolinic acid and M ammonium sulphate, were placed in polystyrene wells and sealed in multicell plates (Linbro) with 0.70ml mother liquor Plates were placed in the dark at 18°C and examined after several days 4.3 Band The human erythrocyte band is a 911 amino acid integral membrane glycoprotein ( M , M 95 000 kD) which catalyzes the one-for-one electroneutral exchange of anions across the erythrocyte membrane [47-49] Mild trypsin treatment of ghost membranes releases a 42kD water soluble N-terminal cytoplasmic fragment The remaining -55 kD membrane-spanning region can transport anions independently from the N-terminus cytoplasmic domain The amino acid sequences of band from mouse [50], chicken [51] and human [52] have been deduced from cDNA sequencing These sequences show high degrees 366 of homology in the membrane-spanning regions which have been predicted to span the bilayer up to 14 times To date, the mechanism of its action and its native structure are not completely understood A complete D high resolution structure would be required to answer these questions Human erythrocyte band represents -25% of the membrane protein weight of erythrocytes and can be easily purified by a differential extraction, ion exchange and affinity chromatography in a variety of different detergents [53] The purified band has been characterized in a variety of different detergents by HPLC[54] to determine the aggregation state of the protein Circular dichroism measurements on the detergent solubilized band have reported small changes in the secondary structure[55] but no changes in the inhibitor binding capabilities [56,57] Calorimetric studies on detergent solubilized band have shown that detergents of intermediate size (C12E8, Cl2Eg) optimally stabilize the protein and therefore these detergent types may also be suitable for crystallization trials [58] Native band and its membrane-spanning region both contain a single extracellular site (asparagine 642) of N-linked glycosylation [59,60] The carbohydrate chain consists of branched and heterogeneous poly-Nacetyllactosamine side chains linked to a single core sugar portion [61] Attempts to crystallize glycosylated band have not been successfbl, possibly due in part to the heterogeneous nature of the native protein The carbohydrate components of intact band and its membrane-spanning region can be removed by treatment with a mixture of endoglycosidase F and glycopeptidase F (N-glycanase) This treatment results in the reduction of heterogeneity in the protein as confirmed by the narrowing of the band protein band on S D S PAGE Reithmeier and co-workers have shown that deglycosylation produces very small changes in the band inhibitor binding capabilities, secondary structure (circular dichroism) and elution profile (HPLC) when compared with the native protein [54], although a similar aggregation state (dimerhetramer) for this and the native band preparation was observed Reithmeier et al [62] have reported small crystals of deglycosylated band in C12E8 using the hanging drop technique with ammonium sulphate as the precipitant at 4°C They found that the choice of detergent and the need for deglycosylation of band was critical for obtaining crystals Although these crystals were rather small (0.15 mm in length) and could only be handled at 4"C, these initial trials represent a significant initial step towards larger samples and possible diffraction studies 4.4 Other proteins The reaction centre from Rhodopseudornonas vividis, has been crystallized completely free of lipids and gives rise to diffraction data and structural 361 resolution which is now well known[63] On the other hand, the B antenna complexes from Rhodomanas acidophila retain high order, diffracting to 2.5 A even though residual lipid is present throughout the purifications and crystallizations (R Cogdell, personal communication) Ca*+-ATPasefrom sarcoplasmic reticulum is rather unstable in detergent and therefore some means of enhancing protein stability will need to be found before crystallization trials can be undertaken Although the protein is found to be stable for some days at 2°C under nitrogen and under special detergent conditions, only two-dimensional clusters of protein of 200 nm-1 pm in diameter were formed [64] Electron microscopic examination by freeze fracture and negative stain shows stacked lamellar arrays of protein interspersed with lipid The purified protein formed similar crystals but with less detergent content, but no role for lipids in this form of the protein could be deduced since a minimum of 10mol of phospholipid per protein was usually retained in this system Relatively high Ca2+ (20mM) and low pH (6.0) is needed for crystallizations, and some anionic-metal ion interactions (to lock the protein in a particular conformation) may be important in electrostatic associations to promote formation of the stacked microcrystallites which were unsuitable for X-ray diffraction Photosystem I reaction centres have been crystallized, but the only phospholipid to induce small crystal formation is lysophosphatidylcholine [65] 4.5 Summary There appear no clear rules, as yet, about whether phospholipids can promote 3D crystal formation of integral membrane proteins Provided that the crystallization milieu is homogeneous, and the contents of this milieu welldefined and controlled, some benefit may result from the addition of lipids during trials However, the type and acyl chain length of such phospholipids are yet two hrther parameters to be varied, and perseverance may, or may not, be rewarded in varying the changes until suitable crystals are formed If they are, then the intellectual challenge to understand the phenomenon remains, with the hope of using the information for hrther examples Small ( M , < 7000) molecule crystallizations in chemical work are almost routine nowadays, soluble proteins are not predictable and membrane proteins present a real challenge to the patient worker Much basic work is still required, not only in terms of the effects of lipids on crystallization phenomena, but also on protein purifications, stability, reconstitutions and hnctional criteria Diffraction and other biophysical methods, including nuclear magnetic resonance, are all useful in describing atomic structural resolution of membrane proteins, and they will become more productive if recombinant DNA methods provide ways of obtaining large (mg) quantities of active proteins 368 Conclusion In the spirit of this volume, we have here tried to identify possible determinants of membrane protein 3D crystallizations and 2D array formation which involve lipid-protein interactions as a potential guide, albeit very scanty at present, for future trials It will be of great interest to observe the area and monitor progress in five or ten years time to see if lipids are indeed important in this kind of work A cknowledgem ents This work was supported through grants from SERC (GR/F/80852; GR/H/ 561552; the EC (SBIOT-9 13023 CVB); the Royal Society, British Council and the Wellcome Trust We wish to thank R Cogdell, R.C Ford, H Michel, R.A.F Reithmeier and J.P Rosenbusch for personal communications and discussions of unpublished data References [l] [2] [3] [4] [5] [6] [7] [8] [9] [lo] [Ill [I21 [I31 [14] [15] [I61 [17] Eisele, J.-L and Rosenbusch, J.P (1990) J Biol Chem 265, 10217-10220 Kuhlbrandt, W (1992) Quart Rev Biophys 25, 1-49 Watts, A and Spooner, P.J.R (1991) Chem Phys Lipids 57, 195-211 Sternberg, B., Gale, P and Watts, A (1989) Biochim Biophys Acta 980, 117-126 Watts, A (1987) J Bioenerg Biomembranes 19, 625-653 Marsh, D and Watts, A (1989) In: Recent Advances in Membrane Fluidity, Vol (Aloia, R., Ed.) pp 163-200, Alan R Liss, New York Michel, H (1990) In: Crystallization of Membrane Proteins (Michel, H., Ed.) ch 3, 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state, 224 functional significance of lipids, 245 high affinity site, 232 lipid selectivity, 240 photoaffinity labelling, 233 reconstitution, 247 acetylchotinesterase, 149 Acholeplusma Zaidluwii, 289, 34 AChR, see acetylcholine receptor actin, 156 actin-binding protein CapZ, 155 acyl-chain covalently linked, 148-150 degree of unsaturation, 247 effect on lipid-protein interaction, 87-1 04 in vivo modification, 91, 92 interdigitation, length, adamantanediazirine, 234 adenylate cyclase, 293 ADP-ATP carrier, 49, 56, 60, 267 aggregation dynamic, 23 of helices and integral proteins, 4, 50, 198 processes, 23, 69 agonist, 228, 249 binding sites, 23 alamethicin, 10 alanine a-helix, 43 amino acid residue distribution, 130 A{-aminobutyricacid (GABA), 260 anaesthetics, 16, 18, 19, 33, 34, 232, 240, 251, 268 anchor principle, 203 androstane, 219, 237, 283 androstanol, 19 angiotensin, 342 annexins, 145 annular lipid, 5, 102, 231, 238-240, 247, 251, 322 shell, 260 sites, 88, 244 annulus, 302 Antipyralazo 111, 286 apocytochrome c, 129, 130, 133, 137, 139-145, 151, 153, 341 arachidonic acid, 249, 263 aromatic amino acids, 206 arrays, 2D, 351, 352 arrestin, 292 ASA, 235 asymmetry, membrane, 354 ATP synthase, 291 atnopeptin 111, 342 attenuated total reflection, 227 azidopyrene, 16, 17 bacteriophages, 191 bacteriorhodopsin, 47, 49, 50, 263, 13, 339, 342, 360, 361,364 band 3, 313, 365, 366 p-barrel, 47, 51 BC3H-I, cell line, 245-25 BDH, see P-hydroxybutyrate dehydrogenase bilayer thickness, 7, 274, 354 binding constant, 134 binding isotherms, 131, 132 bombesin, 342 boundary lipid, 4, 68, 88, 102, 103, 205, 302, 304, 312, 315, 322 brominated lipids, 110, 243, 244 bungarotoxin, 225, 250 C-and N-terminal regions, 198 C-terminal end, 206 part, 195, 196 C-terminus, 20 I , 208 Ca2+,Mg2+-ATPase, 49, 88, 244, 259, 264, 265, 268, 269, 276, 277, 281, 293, 302, 316, 317, 339, 341, 343, 361, 367 from red blood cells, 266, 267 calcineunn 0,149 calcitonin, 340 calcium, 336 calmodulin, 266, 16 calorimeter, AC, 14 372 calorimetry differential scanning, 7-12, 14,16,31,243 volume perturbation, 12-16 carbene, 234 cardiolipin, 56,57,61,71,110,1 11, 122,142, 147,165-167,173,174,195,265,267,290, 343 small unilamellar vesicles, 118 synthase, 70,71,167 cardiotoxin, 342 C12E8,261,265 ceramide, 170 channel conductance, 246,248,263 ion, 213 ligand-gated, 231 charged distribution of residues, 59,60 surface, 206 chemical labelling, 215,220 chemical shift anisotropy, 147 chemically induced dynamic nuclear polarization (CIDNP), 141 chlorpromazine, 232 CHO cells, 186 cholate, 260,279 cholestane, 237 cholesterol, 18, 19,90-92,95, 97, 102,103, 205,222,223,235,238,240,241,244,248, 251,268,289,291 affinity for the acetylcholine receptor, 222 depletion in microsomes, in vitro, 88, 94-96 effect on enzyme kinetics, 88 effect on lipid-protein interaction, 87-1 04 hemisuccinate, 244 incorporation in microsomes in vitro, 88, 91,9496,98-102 in vivo, 88-91,94-96 cholesterol-rich diet, 90 cholesteryl diazoacetate, 235 hemisuccinate, 223,240 choline kinase, 168 cholinephosphohansferases,168 chromatography, high-performance size-exclusion, 200,204 chromosome replication, 164 circular dichroism, 130,151-153, 198-200 Clausius-Clapeyron equation, 12,13 cluster, 8, 15, 17, 29 clycocalyx, cocaine derivatives, 33 coherence length, 20,22 Complex I (NADH-ubiquinone oxidoreductase), 267 Complex 111, 343 conformation, of protein, 15 I , 194 conformational order, of lipid, 19 cooperative phenomena, 3,9, 16,67-83 cooperativity, 6,68-70,72,73,77,80-82 fluctuations, 17 kinetic, 68 correlation length, 2I correlation times, 307 crystallization, 2D,306 cubic phases, 147 cytochrome b,, 294 cytochrome bcl, 292 cytochrome c, 28,49,55-57, 68,113, 128-130, 133, 135, 137,140, 143-147, 153-155, 290,293,343,361 cytochrome oxidase, 155, 293,343 cytoskeleton, 2,4,128 Dansyl-C6-choline, 226 DBI, see double bond index Debye-Hiickel theory of electrolytes, 55 2(-N-decyl)aminonaphthalene-6-sulfonicacid, 81,82 dehydration of membranes, 227 of the lipid surface, 137 surface, 137 deoxycholate, 312 desaturase, 88 desensitization, 248,251 detergent, 232,260 dialysis method, 199 interaction with the acetylcholine receptor, 222 detoxication, 88 diacylglycerol, 76,168 kinase, 70-72 dibucaine, 16,32,33 diet, 293 cholesterol-rich, 90 effects on lipid-protein interactions, 293, 294 dietary studies, 294 diethyl ether effect on protein aggregation, 312 373 differential scanning calorimetry (DSC), 7-12, 14,16,31,243 diffusion, 291 digalactosyl diglyceride, 359 dimyristoylphosphatidic acid (DMPA), 34I dimyristoylphosphatidylcholine (DMPC), 6, 12,13, 15, 17, 18,25,26,28,111, 146, 223,307,355,356,358,360 dimyristoylphosphatidylglycerol (DMPG), 32, 135-138, 142,146, 151,153, 155,157,340 dimyristoylphosphatidylserine (DMPS), 146, 223 dioleoylglycerol (DOG), 70,71,147 dioleoylphosphatidylcholine (DOPC), 219, 247,341,342 dioleoylphosphatidylethanolamine (DOPE), 147 dioleoylphosphatidylglycerol (DOPG), 147 dioleoylphosphatidylserine (DOPS), 1I , 14, 115, 152,153 dipalmitoylphosphatidylcholine (DPPC), 8-1 9, 22,24,30,311, 333,340 diphenylhexatriene (DPH), 95,96,206,290, 307,315, 318 diphtheria toxin, 342 diphytanyl lipids, 44 distearoylphosphatidylcholine (DSPC), 6,12, 13, 15, 17,18,25,26,28 DMPA, see dimyristoylphosphatidic acid DMPC, see dimyristoylphosphatidylcholine DMPG, see dimyristoylphosphatidylglycerol DMPS, see dimyristoylphosphatidylserine DNA replication, 173 DnaA protein, 181 DNS, see 2(-N-decyl)aminonaphthalene-6sulfonic acid docosahexaenoate, 221 DOG, see dioleoylglycerol domains, 4,17,18,27-29,33 transmembrane, 238 DOPC, see dioleoylphosphatidylcholine DOPE, see dioleoylphosphatidylethanolamine DOPG, see dioleoylphosphatidylglycerol DOPS, see dioleoylphosphatidylserine double bond index, 87-104 double recombinants, 155 DPH, see diphenylhexatriene DPPC, see dipalmitoylphosphatidylcholine drugs, 33,34 DSC, see differential scanning calorimetry DSPC, see distearoylphosphatidylcholine Duchenne muscular dystrophy, 294 dynamic heterogeneity, 4,5 protein-lipid network, 207 modelling, 52,199,202,204 egg-phosphatidylcholine, large unilamellar vesicles, 117,1 I9 electron microscopy, 215 electron spin resonance (ESR), 48,55,68,69, 87-104,139,140,218,219,224, 236,239, 243,251,294,302,311, 313 boundary lipid, 219 rotational correlation times, 219 saturation transfer (STEPR), 303 spectra, 95,99,100, 142 spin label, 34,46,88,95, 98,100,102,103, 138, 139,219,236,239 electrostatics mechanism, 79,110, 13I , 134,135 surface, 131 energy barrier, 272 enthalpy, entropy, 7,23 enzymes, 67 EPR, see electron spin resonance equilibrium constant, 271 equilibrium for lipid association, 42 ERITC, see erythrosin isothiocyanate erythrosin isothiocyanate (ERITC), 307,3 14, 317 Escherichia coli, 164,166,171,192,195,263 membrane composition of cell, 208 phospholipid composition of the inner membrane, 208 ESR, see electron spin resonance ethanolamine transferase, 168 ethidium, 226 N-ethylmaleimide, 215 fat-deficient diet, 91 fatty acids, 249 free fatty acids (FFA), 250, 251 regulation on protein function, 249 flip-flop rates, 204 float principle, 203 fluctuations, 4-6, 12-15,21,23,29,30,32 membrane, 17,18 fluid phase, 3,6,24 fluid transition, 7,8,14,336 74 fluidity, 210,271,273, 294, 302, 311-313 effect on protein mobility, 307 of boundary lipid, 12 fluorescence, 5, 27, 31, 110, 113, 115, 117, 119, 122, 137, 138,226,227,236-238 243, 244, 265,282, 290, 310 anisotropy, 95-98 anisotropy decay, 200, 302 quenching, 11 I , 236 quenching titrations, 73 spectroscopy, 95-98 studies of bilayer properties, 95-98 time-resolved, 200, 205, 303, 306, 307, 313 tryptophan, 109, 141, 142, 200 Fourier transform infrared spectroscopy (FTIR), 130, 153,265, 323 advantages, 325 assignment of protein bands, 336, 337 derivation, 22, 153, 198, 200, 227, 323 differential, 329 membrane polar lipids, 33 I quantification of protein secondary structure by, 338, 339 resolution enhancement, 326 free-volume theory, 68 frictional coefficient, 271 fructose-6-phosphate, 74 FTIR spectroscopy, see Fourier-transform infrared spectroscopy functional implications of lipid specificity, 145 fusion, 107 fusion proteins, viral, 343 H+,K+-ATPase, 281 &hairpin, 48, 50, 52 Halobacteriuni halobium, 44, 263 halothane, 16, 18 heat capacity, 8, 10-12 a-helix, 48, 50, 53, 123, 151, 196, 202, 339 alanine, 43 conformation, 123, 134, 171 hydrophobic, 264 transmembrane, 47 0-helix, 44, 45 heterogeneity, 2-6, 11, 12, 17, 19, 23, 26, 9-3 dynamic, 4, 5, 18 hibernation, 294 Hill coefficient, 74, 76, 78, 82, 92, 94, 95, 103 homeostatic, 251 adaptations, 246 homeoviscous adaptation, 294 hydropathy, 15 hydropathy plot, , 63, 89 hydrophilicilipophilic balance, 69 hydrophobic domain, 47, 58, 61, 62, 195, 208, 274 a-helices, 264 matching, 19, 20, 22, 25 thickness, 19, 25 hydrophobic matching, 20, 22, 25 hydrophobic mismatch, 275 hydrostatic pressure, 12 p -1iydroxybutyrate dehydrogenase (BDH), 73-75 R-3-hydroxybutyrate dehydrogenase, 72, 73 G-proteins, 120, 121, 155-157 GALA, 343 gated pore model, 288 gel phase, 3, 6-8, 14, 24, 30, 336 gene V protein, 194 glucose-6-phosphatase, 88 glucose transporter, 291 glucuronidation, 88 glycophorin, 339, 341 glycoprotein 53 kDa, 279 glycosylphosphatidylinositol, 149 Golgi, 164, 174-184 Gouyxhapman diffuse double layer theory, 135 gramicidin, 13, I17 A, 44,45 D, 340 image reconstruction, 15 infrared spectroscopy, see Fourier transform infrared spectroscopy insecticides, 33 interdiffusion, 26 interface activation, 70 enrichment, 25 PK,, 137 region of lipid assemblies, 335 regions, 33 tension, internal reflection element, 227 iodoacetamide spin label (IASL), 304 ion channels, 213, 231, 249 gradients, 115-120 375 ionic screening, 55 isoelectric point, 129, 130, 136 isoprenylation, 149 kinetic cooperativity, 68 Kologornov-Avrami theory, 15 lactalbumins, 128 lactose permease, 69 large unilamellar vesicles (LUV), 8, 12, 15, 16, 116-122 laser Raman spectroscopy, 13, 198, 199 lateral distribution, 21-23 organization, phase separation, see phase separation leucine transport system, 291 ligand gated channel, 23 ligand trapping, 68 light-harvesting chlorophyll &-protein complex, 358, 359 protein complex, 47 lindane, 33 line shape optimized maximum entropy method (LOMEP), 326-328 lipid acyl chains, 333 annulus, see annular lipid association constants, 42, 56 association sites, 42, 50 asymmetry, 244 bilayer thickness, 20 brominated, 141 chain dynamics, 46 dynamics, 302, 322 enrichment, 25-2 first-shell, 239 fluidity, 248, 308 -peptide interaction, 107 phase transition, gel to liquid crystalline, 280 pK, shift, 56 polymorphism, 146, 204, 336 probes, 234, 236, 237 -protein dynamics, 309 -protein interactions, 94, 98, 102-104, 231-252, 260 -protein interface, 216, 219, 220 -protein specificity, 25, 28, 43, 69, 70, 110, 353,354 selectivity, 25, 55, , 142 acetylcholine receptor, 240 specificity, 25, 28, 43, 69, 70, 110, 353, 354 trapping of, 204 lipid asymmetry, 239 lipid exchange, 204 rate, 103 slow, 101 lipopolysaccharide, 356, 364 local structure, 17 LOMPE, see line shape optimized maximum entropy method long-range attraction, lysine, 57, 61, 206 lysophosphatidylcholine, 367 lysophospholipids, 25 lysozyme, 129, 130, 133, 137, 144 MI3 bacteriophage assembly, 204, 207 assembly site of, 193 N-terminal, 195, 196, 201, 202, 208 reproductive life cycle, 192, 194 MI3 coat protein, 49, 52-54, 56, 192, 195 amino acid sequence of, 195 conformation, 43, 197-200 micellar-bound, 20 orientation, 202, 208 reconstitution of, 196, 198, 199 secondary structure, 200 storage, 207 terminal regions, 195, 196, 198, 200-202, 206,208 transmembrane regions, 198 maleimide spin label (MSL), 305, 317 mannose-6-phosphatase, 99 MARCKS, see myristoylated alanine-rich C kinase substrate mastoparans, 120, 121 mattress model, 20-22, 69 melittin, 306, 313, 317, 343 membrane asymmetry, 354 composition of acetylcholine receptor-rich membranes, 22 of Eschekhiu coli cell, 208 fluctuations, 17, 18 heterogeneity, insertion, 108 penetration, 138-142 potential, 15 376 membrane (cont a) proteins 2D-arrays, 351-368 3D crystals, 351-368 spanning domain, 58 topology, 11 viscosity, 293 effect on function, 273 membrane-bound assembly sites, I94 merocyanine 540, 95, 98 mesomorphism, 333 metabolism of phospholipids, 164 methyltransferase, 169 micelles, 260 microscopic modelling, 16-1 microsomes cholesterol-depleted, 90, 1, 96 cholesterol-enriched, 90, 91, 96, 99-102 fat-deficient, 92-94, 96-98, 103 microviscosity, 95 mismatch, 33 mitochondria, 174 complex 111, 342 membrane, 115, 131, 267, 292 presequence, 107 mixed lipid systems, 12 modelling membrane proteins, 242, 244 membranes, 242, 244 phospholipids, 242, 244 molecular dynamics, 52, 199, 202, 204, 13 molecular mechanics, 43 Monte Carlo calculation, , 33 simulation, 16, 44 multilamellar vesicles (MLV), 8, 9, 11-13, 15, 16 mutagenesis, 215, 216 site-directed, 02 myelin basic protein (MBP), 128-141, 144-1 47, 152-1 57 myelin proteolipid, 49, 56 protein, 55, 62 myohaemerythrin, 241 myristoylated alanine-rich C kinase substrate (MARCKS), 13 myristoylation, 149 N-terminal, 195 part, 196 region, 201 N-terminus, 202, 208 Na' ,K+-ATPase, 49, 55, 56, 259, 267, 279, 281, 283,288, 359, 360 a subunit, 61 p subunit, 62 Nai,Mg2+-ATPase, 289 nAChR, see nicotinic acetylcholine receptor neuroreceptor, 231 a-neurotoxins, 23 nicotinic acetylcholine receptor, 21 3-228, 324 nicotinic acetylcholine receptor, see also acetylcholine receptor nicotinic acetylcholine receptor affinity ligands, 214, 215, 226 lipids, 222 spin labels, 219, 220 agonist, 214, 215, 226, 227 C-terminus, 15 conformational states, 214, 224 desensitized state, 214, 215, 225 resting state, 214 flux, 223, 226 function, 214, 222-225 kinetics, 214, 224-228 rate constants, 14, 15, 224 lipid bilayers, 223 acyl chain saturation, 223 phospholipid head group, 223 lipid environment, 221, 222 lipid selectivity, 220 MI, 215, 216, 220 M2, 215, 216, 220 M3, 215-218, 220 M4, 217, 218, 220 MA, 217 N-terminus, 215 reconstitution, 219 structure, 215, 218, 227,228 transmembrane helices, 215, 18, 220 nitrobenzooxadiazole (NBD), 282 p-nitrophenol, 89-1 04 NMR, see nuclear magnetic resonance non-annular sites, 244 non-bilayer structures, 146, 147, 204 non-competitive antagonists (NCI), 232 non-equilibrium system, 27 nuclear magnetic resonance, 153, 154, 201, 202 2D spectroscopy, 198 'H, 154 377 nuclear magnetic resonance (cont ) 2H, 46, 112, 146, 154,206 high-resolution, 201 3'P, 147, 154, 206, 352 solid state, 201 oleic acid, 147 oligomerization, of helices and integral proteins, 50 OmpA, 171 order parameter, 19, 95, 100, 223, 307, 308 packing, knobs-into-holes, 204 palmitic acid, 142, 222 palmitoylation, 149 paramagnetic quenching, 236 pannaric acid, trans, 95, 97, 98 Partial Least Squares, 338 partition coefficient, 33 patch-clamp technique, 245-25 pentagastrin, 109 pentalysine, 146 peptide translocation, 15-120 peptides, model, 108 perimeter, intramembranous, 49 peripheral integral protein interaction, 154, 155 membrane proteins, 128-158 protein, 128 permeability, passive, 18 PH gradient, 115 titration of lipid selectivity, 56 phage assembly, 207 phase diagram, 6, 22-24 hexagonal, 146, 147, 204 separation, 3, 4, 19, 23, 32, 95, 97, 146, 239 separation, gel to liquid crystalline, 280 transition, 3, 7, 8, 10, 12, 14-18, 23, 30, 95, 96, 98, 100, 264, 290, 294, 311, 333, 336 transition, first-order, phoE gene product, 17I , 343 phosphatidic acid, 56, 72, 219, 223, 265, 269, 29 phosphatidylcholine (PC), 2, 10, 13-19, 22, 24-26, 28, 30, 31, 56, 71, 72, 74, 75, 80, 89, 90, 92, 93, 103, 110, 111, 114, 115, 119, 140, 142, 169, 174, 17&178, 181, 184, 219,220,222,236, 241,244246,264,269, 274, 277, 278, 281, 283 biosynthesis, 175 biosynthetic activity, 178 biosynthetic pathways, 179, 180 serine, 29 unilamellar vesicles large (LUV), 121 small (SUV), 118 phosphatidylethanolamine (PE), 29, 56, 70, 89-93, 142, 147, 165, 167, 178, 179, 222, 242,244,245,247, 265, 277,278, 287,293, 294, 363 di-methylated (PDME), 167, 177, 178 mono-methylated (PMME), 167, 169 phosphatidylglycerol (PG), 56, 80, 153, 165-167, 171, 174, 195, 278, 287, 291 depleted cells, 172 phosphatidylglycerophosphate,360, 361, 364 phosphatidylinositol (PI), 89-93, 142, 167, 169, 174, 176, 177, 181, 184, 244, 245, 247, 263, 289, 293 biosynthesis, 178 phosphatidylinositol/phosphatidylcholine hypothesis, 184 phosphatidylserine (PS), 28, 56, 75-77, 92, 93, 115, 131, 139, 142, 145, 166, 167, 219, 220,223, 244, 245,247,265,293, 336, 340 decarboxylase, 165 synthase, 165, 169 phosphodiesterase cGMP, 292 phospholamban, 317 phospholipase, 249 A*, 4, 28-33, 138, 145, 251 C, 150, 245 phospholipid, 163, 23 1-240 chain length, 274 composition, 260 composition of the inner membrane of E coli, 195 environment, 269 headgroup region, 206 negatively charged, 265 perturbations introduced by proteins in, 339 transfer protein, 175 vesicles, 108 phosphorescence anisotropy, time-resolved (TPA), 303, 311, 313, 317 phosphorylcholine, 73 photoaffinity labelling acetylcholine receptor, 233 photochemical crosslinking, 140, 141 photolabelling, 141, 215, 216, 233 378 photoreceptor membranes, 354 photosynthetic reaction centre, 44, 50, 62, 274 hydrophobic stretches L and M subunits, 62 photosystem I, 367 reaction centre, 357, 358 pK, shift of lipid, 56 polarization ratio, 97 0-polymerization process, 198 polyarginine, 135 polylysine, 135, 144, 146, 147 polymorphism, see lipid - polymorphism, 146, 204, 336 polyunsaturated fatty acids, 294 porin, 47,363, 364 porins, bacterial, 355-357 positive-inside rule, 57 presequence, mitochondria, 107 pressure, surface, 275 profilin, 184 proportion of gauche rotamers, 334 prostaglandins, 263 protein aggregation, 22, 23, 27, 64, 204, 31&315 effects of diethyl ether, 312 conformation, 15I , 197 conformational changes, 194 crosslinking, 13 density, 354 detergent interactions, 353 domains, 273 dynamics, 302 hydrophobic interface, 35 insertion, 107, 206 kinase, 28, 29, 75-80, 131, 133, 145 -lipid interaction, 128, 204, 208 network, dynamic, 207 mobility relationship to lipid fluidity, 307 orientation, 196,208 packing knobs-into-holes, 204 ridges-into-grooves, 204 precursor, 107 -protein interaction, 21, 28, 194, 202, 208, 310, 313 reconstitution, 208 rotation, effect on function of, 10 rotational, 308 rotational diffusion, 307 rotational mobility, 11 , 12 relationship to function, 11 secondary structure, 53, 54, 200, 338, 339 sequence, stability, 222 structure perturbation induced by lipids, 339, 342 transition, first order, 10, 12 proteolipid apoprotein (PLP), 155, 157 DM-20, 62 prothrombin, 128 purple membranes, 44, 354 pyrene, 95, 97 pyrene- 1-sulfonyl azide, 233 pyrenemaleimide, 16 pyruvate oxidase, 79-82 quinacrine, 226 Raman spectroscopy, 13, 200 receptors acetylcholine, 49, 56, 69, 88, 213-228, 23 1-252 0-adrenergic, 265 hormonal, 157 second messenger (see also G-proteins), 157 reconstituted ion, 269 reconstitution, 6, 70, 199, 200, 219, 222-224, 259, 260,265, 342 acetylcholine receptor, 219, 222, 247 affinity chromatography, 222, 223 Ca++-Mg++-ATPase, 302 procedures, 196, 199, 200, 208 regulations by phospholipids, 164 relaxation kinetics, 13 Rhodobacfersphaeroides, 62 Rhodopseudomonas viridis, 44, 62, 366 rhodopsin, 47, 49, 56, 58, 59, 289, 291, 342 rhodopsin kinase, 292 Saccharomyces cerevisae, 168, 169, 171, 177 sarcoplasmic reticulum (SR), 278, 302, 16, 34 saturation binding, 130 saturation transfer electron paramagnetic resonance (STEPR), 303, 305-307, 317 SECBp, 182-1 84 SEC14p, 178, 18&182, 184 SecA, 172 SecE, 172 SecY, 172 379 secretion, 1-1 73 selectivity of lipid interaction, 25-27, 55-57, 264-268 see also lipid-protein selectivity selectivity sequence, 142-144 self-activation, 72 0-sheet, 47, 50-53, 64, 151, 196, 339, 342 signal peptides, 342 signal transduction, 23 simian immunodeficiency virus, 343 small unilamellar vesicles (SUV), 7, 8, 10-12 cardiolipin, 118 phosphatidylcholine, 118 solvation lipid, 68 solvent static effects of, 270 solvent viscosity, 271, 272 specific heat, 17, 18 spectral deconvolution, 99-1 02 spectrin, 131 spectroscopy, differential, 329 sphingomyelin, 92, 244, 245 sphingosine, 170 spin labels, 98-102, 142, 218, 236, 239, 302, 303, 309, 310, 317 androstane, 237 cholestane, 237 stearic acid, 56, 219 spin labels, 237 STEPR, see saturation transfer electron paramagnetic resonance Stern-Volmer equation, 237 steroids, 247 stoichiometry, lipid-protein, 42, 48-52, 64, 129, 131, 135, 136, 139, 140, 243 sugar transport, 164 surface area, dehydration, 137 electrostatics, 131 pressure, 275 tension, 277 interfacial, 276 TFA, see fluorescence and transient fluorescence thapsigargin, 282 thickness of a bilayer, 274, 354 toxin, 141, 232 tetanus, 140 transducin, 149, 292 transient fluorescence anisotropy (TFA), 303, 306, 307, 313 transition, 7, 9, 12, 30, 32 see also phase transition transition state theory, 269 transmembrane domains of proteins, 196 signalling, 156-158 transmembrane a-helix, 47, 51 transmission coefficient, 270, 27 trapping lipids, 204 model, 77 ttiacylglycerol, 90, 92 trifluoromethyl-3-iodophenyl ['251]TID, 217 3-(trifluoromethyl)-3-rn-iodophenyldiazirine (TID), 235, 236 trinitrobenzenesulphonate (TNBS), 245 Triton X-100, 265 P-turn, 48 ubiquinone, 292 UDP-glucuronyl transferase (UDPGT), 88, 94, 98, 102, 103 kinetic behaviour, 88, 90-94, 102 reaction mechanism, 89 UDPGT, see UDP-glucuronyl transferase valinomycin, I 6, 117, 12 1, 122 van der Waals interactions, 7, 21, 73 vanadate, 282, 306 vesicles, asymmetric, 18 vinculin, 343 viruses, 191 viscosity, 271 membrane, 294, 307, 308 wetting, 27 X-ray diffraction, 13, 46, 70, 199, 274 xenobiotic compounds, 88 yeast, 168, 169, 171, 177 ... which tends to randomize the protein distribution; (iii) proteinlipid interactions and lipid- mediated protein- protein interactions; and (iv) direct protein- protein interactions which may be of.. .Protein- Lipid Interactions Editor A Watts Department of Biochemistry, University of Oxford, Oxford, OX1 3QU United Kingdom 1993 ELSEVIER Amsterdam London New York Tokyo New Comprehensive Biochemistry. .. the influence of the lipid- bilayer structure on the hnctioning of certain enzymes In particular, we shall address cooperative effects due to lipid- lipid and protein- lipid interactions, which may