Determining membrane protein structures: still a challenge!

Determination of structures and dynamics events of transmembrane proteins is important for the understanding of their function. Analysis of such events requires high-resolution 3D structures of the different conformations coupled with molecular dynamics analyses describing the conformational pathways. However, the solution of 3D structures of transmembrane proteins at atomic level remains a particular challenge for structural biochemists--the need for purified and functional transmembrane proteins causes a 'bottleneck'. There are various ways to obtain 3D structures: X-ray diffraction, electron microscopy, NMR and modelling; these methods are not used exclusively of each other, and the chosen combination depends on several criteria. Progress in this field will improve knowledge of ligand-induced activation and inhibition of membrane proteins in addition to aiding the design of membrane-protein-targeted drugs.

[1]  M. Krauss,et al.  Dynamics of proton transfer in bacteriorhodopsin. , 2004, Journal of the American Chemical Society.

[2]  C. Dominguez,et al.  HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. , 2003, Journal of the American Chemical Society.

[3]  Peteris Prusis,et al.  Prediction of indirect interactions in proteins , 2006, BMC Bioinformatics.

[4]  Y. Sanejouand,et al.  Dynamical properties of the MscL of Escherichia coli: a normal mode analysis. , 2003, Journal of molecular biology.

[5]  R. Kim Transporters and drug discovery: why, when, and how. , 2006, Molecular pharmaceutics.

[6]  R. Guérois,et al.  Dodecylphosphocholine micelles as a membrane-like environment: new results from NMR relaxation and paramagnetic relaxation enhancement analysis , 1998, European Biophysics Journal.

[7]  Klaus Schulten,et al.  Molecular dynamics simulations of proteins in lipid bilayers. , 2005, Current opinion in structural biology.

[8]  Claudio N. Cavasotto,et al.  Structure-based development of target-specific compound libraries. , 2006, Drug discovery today.

[9]  J. R. Meer Analytics with engineered bacterial bioreporter strains and systems. , 2006 .

[10]  J. Baenziger,et al.  A rapid method for assessing lipid:protein and detergent:protein ratios in membrane-protein crystallization. , 2003, Acta crystallographica. Section D, Biological crystallography.

[11]  Robert Preissner,et al.  Analysis and prediction of helix–helix interactions in membrane channels and transporters , 2006, Proteins.

[12]  O. Pongs,et al.  Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR , 2006, Nature.

[13]  R. MacKinnon,et al.  Phospholipids and the origin of cationic gating charges in voltage sensors , 2006, Nature.

[14]  J. Rosenbusch,et al.  Lipidic cubic phases: a novel concept for the crystallization of membrane proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Baker,et al.  Multipass membrane protein structure prediction using Rosetta , 2005, Proteins.

[16]  N. Unwin,et al.  Refined structure of the nicotinic acetylcholine receptor at 4A resolution. , 2005, Journal of molecular biology.

[17]  A. Milon,et al.  Heterologous expression of G-protein-coupled receptors: comparison of expression systems from the standpoint of large-scale production and purification , 2003, Cellular and Molecular Life Sciences CMLS.

[18]  R. Henderson,et al.  Three-dimensional structure determination by electron microscopy of two-dimensional crystals. , 1982, Progress in biophysics and molecular biology.

[19]  J. Møller,et al.  Interaction of membrane proteins and lipids with solubilizing detergents. , 2000, Biochimica et biophysica acta.

[20]  Krzysztof Palczewski,et al.  The crystallographic model of rhodopsin and its use in studies of other G protein-coupled receptors. , 2003, Annual review of biophysics and biomolecular structure.

[21]  Francesca Fanelli,et al.  Quaternary structure predictions of transmembrane proteins starting from the monomer: a docking-based approach , 2006, BMC Bioinformatics.

[22]  G. N. Sastry,et al.  Recent advances in molecular modeling and medicinal chemistry aspects of phospho-glycoprotein. , 2006, Current drug metabolism.

[23]  P. Nissen,et al.  Modulatory and catalytic modes of ATP binding by the calcium pump , 2006, The EMBO journal.

[24]  G. Rummel,et al.  Detergent binding in trigonal crystals of OmpF porin from Escherichia coli. , 1998, Biochimie.

[25]  K Wüthrich,et al.  Transverse relaxation-optimized NMR spectroscopy with the outer membrane protein OmpX in dihexanoyl phosphatidylcholine micelles , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  S. Buckingham,et al.  Oocytes as an expression system for studying receptor/channel targets of drugs and pesticides. , 2006, Methods in molecular biology.

[27]  R. Henderson,et al.  Three-dimensional model of purple membrane obtained by electron microscopy , 1975, Nature.

[28]  R. Prosser,et al.  Current applications of bicelles in NMR studies of membrane-associated amphiphiles and proteins. , 2006, Biochemistry.

[29]  A F Smeijers,et al.  Coarse-grained transmembrane proteins: hydrophobic matching, aggregation, and their effect on fusion. , 2006, The journal of physical chemistry. B.

[30]  J. Kiehn,et al.  The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications. , 2006, Current pharmaceutical design.

[31]  Paul Curnow,et al.  Membrane proteins, lipids and detergents: not just a soap opera. , 2004, Biochimica et biophysica acta.

[32]  M. Heel,et al.  Voltage-gated K+ channel from mammalian brain: 3D structure at 18 Å of the complete (α)4(β)4 complex , 2003 .

[33]  Dora M Schnur,et al.  Are target-family-privileged substructures truly privileged? , 2006, Journal of medicinal chemistry.

[34]  Michael J Sutcliffe,et al.  Drug Binding Interactions in the Inner Cavity of hERG Channels: Molecular Insights from Structure-Activity Relationships of Clofilium and Ibutilide Analogs , 2006, Molecular Pharmacology.

[35]  R. Henderson Realizing the potential of electron cryo-microscopy , 2004, Quarterly Reviews of Biophysics.

[36]  C. Hunte,et al.  Specific protein-lipid interactions in membrane proteins. , 2005, Biochemical Society transactions.

[37]  Yang Zhang,et al.  Structure Modeling of All Identified G Protein–Coupled Receptors in the Human Genome , 2006, PLoS Comput. Biol..

[38]  Arnaud Ducruix,et al.  Crystallization of Nucleic Acids and Proteins: A practical Approach , 1998 .

[39]  M. Wiener,et al.  A pedestrian guide to membrane protein crystallization. , 2004, Methods.

[40]  Yuanzi Hua,et al.  Cloning and expression of multiple integral membrane proteins from Mycobacterium tuberculosis in Escherichia coli , 2005, Protein science : a publication of the Protein Society.

[41]  Tim J Stevens,et al.  Membrane proteins: the 'Wild West' of structural biology. , 2003, Trends in biochemical sciences.

[42]  H. Michel,et al.  Crystallisation of membrane proteins mediated by antibody fragments. , 2002, Current opinion in structural biology.

[43]  J Andrew McCammon,et al.  A gating mechanism proposed from a simulation of a human alpha7 nicotinic acetylcholine receptor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  C. Sanders,et al.  NMR assignments for a helical 40 kDa membrane protein. , 2004, Journal of the American Chemical Society.

[45]  Peter J Bond,et al.  Insertion and assembly of membrane proteins via simulation. , 2006, Journal of the American Chemical Society.

[46]  H. Michel,et al.  Crystallization of membrane proteins. , 1983, Current opinion in structural biology.

[47]  J. Lacapère,et al.  Two-dimensional crystallization of Ca-ATPase by detergent removal. , 1998, Biophysical journal.

[48]  Fred J Sigworth,et al.  Three‐dimensional structure of the type 1 inositol 1,4,5‐trisphosphate receptor at 24 Å resolution , 2002, The EMBO journal.

[49]  Patrick Jimonet,et al.  Strategies for designing GPCR-focused libraries and screening sets. , 2004, Current opinion in drug discovery & development.

[50]  M. Burghammer,et al.  Crystals of native and modified bovine rhodopsins and their heavy atom derivatives. , 2004, Journal of molecular biology.

[51]  A. G. Brevern,et al.  A structural model of a seven-transmembrane helix receptor: the Duffy antigen/receptor for chemokine (DARC). , 2005, Biochimica et biophysica acta.

[52]  Eva Pebay-Peyroula,et al.  Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside , 2003, Nature.

[53]  Arnaud Ducruix,et al.  Crystallization of nucleic acids and proteins , 1992 .

[54]  Sebastian Doniach,et al.  Expression, purification, and characterization of Thermotoga maritima membrane proteins for structure determination , 2006, Protein science : a publication of the Protein Society.

[55]  Weiliang Zhu,et al.  Molecular dynamics of nicotinic acetylcholine receptor correlating biological functions. , 2006, Current protein & peptide science.

[56]  Peter Nollert,et al.  Crystallization of membrane proteins in cubo. , 2002, Methods in enzymology.

[57]  G. Madhavi Sastry,et al.  Homology modeling of membrane proteins: A critical assessment , 2006, Comput. Biol. Chem..

[58]  Reinhard Grisshammer,et al.  Understanding recombinant expression of membrane proteins. , 2006, Current opinion in biotechnology.

[59]  A Nevzorov,et al.  Structure determination of membrane proteins by NMR spectroscopy. , 2002, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[60]  V. Kasho,et al.  Sequence alignment and homology threading reveals prokaryotic and eukaryotic proteins similar to lactose permease. , 2006, Journal of molecular biology.

[61]  J. Betton,et al.  High throughput cloning and expression strategies for protein production. , 2004, Biochimie.

[62]  Wei Yang,et al.  Protein–nucleic acid interactions: from A(rgonaute) to X(PF) , 2006 .

[63]  Sarel J Fleishman,et al.  Transmembrane protein structures without X-rays. , 2006, Trends in biochemical sciences.

[64]  D. D. Thomas,et al.  Mapping the interaction surface of a membrane protein: unveiling the conformational switch of phospholamban in calcium pump regulation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Jonathan G. Lees,et al.  Analyses of circular dichroism spectra of membrane proteins , 2003, Protein science : a publication of the Protein Society.

[66]  J. Popot,et al.  An atypical haem in the cytochrome b6f complex , 2003, Nature.

[67]  V. Dötsch,et al.  Cell‐free expression as an emerging technique for the large scale production of integral membrane protein , 2006, The FEBS journal.

[68]  S. Harrison,et al.  Lipid–protein interactions in double-layered two-dimensional AQP0 crystals , 2005, Nature.

[69]  Roland Riek,et al.  NMR Structure of Mistic, a Membrane-Integrating Protein for Membrane Protein Expression , 2005, Science.

[70]  P. Nordlund,et al.  An efficient strategy for high‐throughput expression screening of recombinant integral membrane proteins , 2005, Protein science : a publication of the Protein Society.

[71]  Hau B. Nguyen,et al.  Comprehensive evaluation of solution nuclear magnetic resonance spectroscopy sample preparation for helical integral membrane proteins , 2006, Journal of Structural and Functional Genomics.

[72]  F. Baleux,et al.  Concerted influence of key amino acids on the lipid binding properties of a single-spanning membrane protein: NMR and mutational analysis. , 2001, Biochemistry.

[73]  D. Stokes,et al.  Three-dimensional crystals of Ca2+-ATPase from sarcoplasmic reticulum: merging electron diffraction tilt series and imaging the (h, k, 0) projection. , 1998, Journal of molecular biology.

[74]  A. Watts Solid-state NMR in drug design and discovery for membrane-embedded targets , 2005, Nature Reviews Drug Discovery.

[75]  N. Ben-Tal,et al.  Progress in structure prediction of α-helical membrane proteins , 2006 .

[76]  W. Chiu,et al.  Structure of the voltage-gated L-type Ca2+ channel by electron cryomicroscopy , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[77]  James E. Bray,et al.  High-throughput production of prokaryotic membrane proteins , 2005, Journal of Structural and Functional Genomics.

[78]  Konrad Hinsen,et al.  Normal mode-based fitting of atomic structure into electron density maps: application to sarcoplasmic reticulum Ca-ATPase. , 2005, Biophysical journal.

[79]  F. Baneyx,et al.  Recombinant protein folding and misfolding in Escherichia coli , 2004, Nature Biotechnology.

[80]  J. Rosenbusch,et al.  High-resolution structures and dynamics of membrane protein--lipid complexes: a critique. , 2001, Current opinion in structural biology.

[81]  G. Mosser,et al.  Two-dimensional crystallogenesis of transmembrane proteins. , 2001, Micron.

[82]  Paul D Allen,et al.  Structural characterization of the RyR1-FKBP12 interaction. , 2006, Journal of molecular biology.

[83]  S. Opella,et al.  NMR structure determination of a membrane protein with two transmembrane helices in micelles: MerF of the bacterial mercury detoxification system. , 2005, Biochemistry.

[84]  J. Robert,et al.  Efficient solubilization and purification of the gastric H+, K+-ATPase for functional and structural studies. , 2000, The Biochemical journal.

[85]  B. Corry An energy-efficient gating mechanism in the acetylcholine receptor channel suggested by molecular and Brownian dynamics. , 2006, Biophysical journal.