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SPRINGER BRIEFS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY Jordi H. Borrell Òscar Domènech Kevin M.W. Keough Membrane Protein—Lipid Interactions: Physics and Chemistry in the Bilayer 123 SpringerBriefs in Biochemistry and Molecular Biology More information about this series at http://www.springer.com/series/10196 Jordi H. Borrell · Òscar Domènech Kevin M.W. Keough Membrane Protein—Lipid Interactions: Physics and Chemistry in the Bilayer 1 3 Jordi H. Borrell Kevin M.W. Keough Institut de Nanociència i Nanotecnologia Alberta Prion Research Institute Universitat de Barcelona Alberta Innovates Bio Solutions Barcelona Edmonton Spain AB Canada Òscar Domènech Institut de Nanociència i Nanotecnologia and Universitat de Barcelona Barcelona Department of Biochemistry Spain Memorial University of Newfoundland St.John’s NL Canada ISSN 2211-9353 ISSN 2211-9361 (electronic) SpringerBriefs in Biochemistry and Molecular Biology ISBN 978-3-319-30275-1 ISBN 978-3-319-30277-5 (eBook) DOI 10.1007/978-3-319-30277-5 Library of Congress Control Number: 2016933217 © The Author(s) 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland Foreword This book is primarily intended for two kinds of audiences: students from biological sciences who desire a quick entry into the area of lipid–protein membrane interac- tions; and, students from physics or chemistry interested in the physical chemistry underpinning lipid–membrane protein interactions. The book has been conceived as an extension for these undergraduate students and as an introduction to the subject for graduate students who want to enter into membrane research. The objective is to provide a basic background in the physicochemical principles and experimental approaches that are particularly relevant to membrane science. In the first two chapters, we cover elementary topics on lipid and protein biophysical c hemistry, self-segregated structures, and experimental methods currently used in membrane research. Although several membrane proteins are mentioned, we chose l actose permease from Escherichia coli to introduce most of our experimental examples on lipid–protein structures. Chapters 3 and 4 review the most widespread ideas that have emerged from experimental evidence on lipid–protein interactions. Hydrophobic matching, in which integral membrane proteins induce lipids of the bilayer to adjust hydrocarbon thickness to match the length of the hydrophobic sur- face of the protein, and the curvature stress lead to the introduction of the so-called surface flexible model for biomembranes. In chapter 4 we provide several examples of correlations of physicochemical properties of lipids with membrane structure, correct folding and function. For methods to assess lipid–protein interactions (DSC, EPR, X-ray crystallography, electron microscopy), the reader is directed to specific references listed at the end of the chapter. The relatively new technique of using AFM-single-molecule force spectroscopy to investigate lipid protein interactions is introduced in Chap. 4. The purpose of this book is to provide students with an introduction to the physical chemistry of lipid-protein interactions to enable them to extend their studies in this field. v Acknowledgments We wish to thankfully acknowledge the comments and suggestions of the f ollowing people, who have reviewed the manuscript at various stages during its production: Dr. Luis M. Loura, University of Coimbra; and Dr. M. Teresa Montero, Dr. Cristina Minguillón, Dr. Antoni Morros, and Dr. Javier Luque, University of Barcelona: Dr. Manuel Prieto, Centro de Química-Física Molecular, Lisboa for the develop- ment of the FRET formalism reviewed in this book: Dr. Mikhail Bogdanov and Dr. William Dowhan from the University of Texas; Dr. Pierre-Emmanuel Milhiet from the Centre de Biologie Structurale de Montpellier; and, Dr. Daniel J. Müller from the ETH of Zürich for figures and AFM images from their work. Thanks are also due to our editor, Thijs van Vlijmen at Springer-Verlag, for the patience and the encouraging comments. Special thanks go to Dr. Lee D. Leserman, Centre de d’Immunologie de Marseille, Luminy (France), for the privilege of working closely in his lab, long time ago and to Dr. Ronald H. Kaback, University of California Los Angeles (USA), for teaching the lessons learnt from lactose permease. Barcelona (S) Edmonton (CDN) December 2015 vii Contents 1 Molecular Membrane Biochemistry ............................ 1 1.1 Membrane Architecture ................................... 1 1.2 Chemistry and Physics of Membrane Lipids ................... 3 1.3 Membrane Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.3.1 Protein Structure ................................... 6 1.3.2 Membrane Protein Structure ......................... 13 1.3.3 Membrane Protein Insertion in Natural Membranes ....... 16 1.3.4 Hydrophobic Effect and Protein Folding ................ 18 1.4 Micro- and Nanostructure of Biomembranes ................... 24 References .................................................. 27 2 Physicochemical Properties of Lipids and Macromolecules in Higher Level Organization .................................. 31 2.1 Lipid Monolayers at the Interface: Two Dimensional Structures .... 31 2.1.1 Phases at the Air Water Interface ...................... 32 2.1.2 Monolayer Compressibility .......................... 34 2.1.3 Mixing Properties of the Monolayers at the Interface ...... 35 2.2 Langmuir-Blodgett Films .................................. 36 2.3 Structures at the Air-Water Interface ......................... 37 2.3.1 Brewster Angle Microscopy .......................... 37 2.3.2 Atomic-Force Microscopy (AFM) ..................... 38 2.4 Protein- and Peptide-Lipid Interactions in Monolayers ........... 39 2.4.1 Interfacial Studies for Understanding Enzyme Activity ..... 40 2.4.2 Adsorption of Soluble Proteins to Lipid Monolayers ...... 41 2.4.3 Peptide Interaction with Monolayers ................... 42 2.4.4 The Membrane Associated Surfactant Proteins ........... 43 2.5 Structures of Lipids in Aqueous Environments ................. 45 2.5.1 Hydrophobic Effect and Lipid Self-aggregates ........... 47 2.5.2 Liposomes ....................................... 49 2.5.3 Supported Membrane Systems ........................ 49 ix x Contents 2.5.4 Giant Unilamellar Vesicles (GUVs) .................... 49 2.5.5 Bilayer Compressibility and Bilayer Surface Pressure ..... 51 2.6 The Lipid-Phase Transition: Some Experimental Approaches ..... 52 2.6.1 Differential Scanning Calorimetry of Lipids ............. 52 2.6.2 Fluorescence Anisotropy ............................ 53 2.6.3 31P-Nuclear Magnetic Resonance Spectroscopy .......... 56 2.6.4 AFM in Force Spectroscopy (FS) Mode ................ 58 References .................................................. 59 3 Lateral Distribution of Membrane Components and Transient Lipid-Protein Structures ...................................... 63 3.1 Lateral Distribution in Reconstituted Systems .................. 63 3.2 Lipid Phase Separation and Phase Diagrams of Lipid Mixtures .... 65 3.3 Lateral Segregation of IMPs: Experimental Evidence ............ 70 3.4 Boundary, Non-boundary and Bulk Lipids .................... 76 3.5 Hydrophobic Match and Mistmach .......................... 81 3.6 Curvature Stress and the Fluid Surface Model .................. 84 3.7 Lipid Rafts ............................................. 85 References .................................................. 85 4 Dependence of Protein Membrane Mechanisms on Specific Physicochemical Lipid Properties .............................. 89 4.1 Gibbs Energy and ATP Synthesis: The Lipid Coupling ........... 89 4.2 Protein Activity Related to Specific Phospholipids .............. 93 4.3 Dependence of Protein Activity on Lipid Packing, Order Parameter and Temperature ........................... 98 4.4 Interactions of Lung Surfactant Through Lipid Monolayers ....... 102 4.5 The Lipid-Protein Interface ................................ 103 4.6 Thermodynamic Framework and Nanomechanics of IMP Activity .......................................... 107 4.7 Identification of Lipids at the Membrane Lipid-Protein Interface ............................................... 110 4.8 An Integrative Model for Lactose Permease ................... 113 4.9 A Word on Multidrug Resistance Mediated by Membranes ....... 114 References .................................................. 114 Acronyms AFM Atomic Force Microscopy ATR-FTIR Attenuated Total Internal Reflectance Infrared Spectroscopy BAM Brewster Angle Microscopy BDH D-β-Hydroxybutyrate Dehydrogenase Br Bacteriorhodopsin CMC Critical Micellar Concentration DSC Differential Scanning Calorimetry EM Electron Microscopy EPR Electron Paramagnetic Resonance FCS Fluorescent Correlation Spectroscopy FF-EM Freeze-Fracture Electron Microscopy F-MMM Fluid Mosaic Membrane Model FRET Förster Resonance Energy Transfer GFP Green Fluorescence Protein GUVs Giant Unilamellar Vesicles IMPs Integral Membrane Proteins LacY Lactose Permease of E. coli LBs Langmuir–Blodgett Films LPR Lipid-to-Protein Ratio LUVs Large Unilamellar Vesicles MIP Maximum Insertion Pressure MLVs Multilamellar Vesicles MPs Membrane Proteins PLSs Phospholipases 31-P-NMR Nuclear Magnetic Resonance of 31 P PMPs Peripheral Membrane Proteins Rho Rhodopsin SFM Surface Flexible Model SLBs Supported Lipid Bilayers STM Scanning Tunneling Microscopy xi

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