Solution NMR of membrane proteins: practice and challenges

This review focuses upon the application of solution NMR methods to multispan integral membrane proteins, particularly with respect to determination of global folds by this approach. Practical methods are described along with the special difficulties that confront the application of solution NMR to proteins that dwell in the netherworld of the lipid bilayer. Copyright © 2006 John Wiley & Sons, Ltd.

[1]  R. Hodges,et al.  Effect of trifluoroethanol on protein secondary structure: an NMR and CD study using a synthetic actin peptide. , 1992, Biochemistry.

[2]  J. Klein-Seetharaman,et al.  Differential dynamics in the G protein-coupled receptor rhodopsin revealed by solution NMR. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J U Bowie,et al.  Building a Thermostable Membrane Protein* , 2000, The Journal of Biological Chemistry.

[4]  A. McGuire,et al.  Internal and overall motions of the translation factor eIF4E: Cap binding and insertion in a CHAPS detergent micelle , 1998, Journal of biomolecular NMR.

[5]  A. Bax,et al.  A simple apparatus for generating stretched polyacrylamide gels, yielding uniform alignment of proteins and detergent micelles* , 2001, Journal of biomolecular NMR.

[6]  C. Sanders,et al.  Topology and secondary structure of the N-terminal domain of diacylglycerol kinase. , 2002, Biochemistry.

[7]  L. Lian,et al.  Labelling approaches for protein structural studies by solution-state and solid-state NMR , 2001 .

[8]  V. V. Kumar,et al.  Lanthanide-induced phosphorus-31 NMR downfield chemical shifts of lysophosphatidylcholines are sensitive to lysophospholipid critical micelle concentration. , 1991, Biophysical journal.

[9]  P. Schmieder,et al.  Heteronuclear Multidimensional NMR Spectroscopy of Solubilized Membrane Proteins: Resonance Assignment of Native Bacteriorhodopsin , 2002, Chembiochem : a European journal of chemical biology.

[10]  D. Mierke,et al.  Peptide hormone binding to G‐protein‐coupled receptors: Structural characterization via NMR techniques , 2001, Medicinal research reviews.

[11]  A. Bax,et al.  Characterization of Phospholipid Mixed Micelles by Translational Diffusion , 2004, Journal of biomolecular NMR.

[12]  D. W. Bolen,et al.  Protein stabilization by naturally occurring osmolytes. , 2001, Methods in molecular biology.

[13]  L. Kay,et al.  The integral membrane enzyme PagP alternates between two dynamically distinct states. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Otzen,et al.  Using micellar mole fractions to assess membrane protein stability in mixed micelles. , 2005, Biochimica et biophysica acta.

[15]  P. Domaille,et al.  An Approach to the Structure Determination of Larger Proteins Using Triple Resonance NMR Experiments in Conjunction with Random Fractional Deuteration , 1996 .

[16]  G. Otting,et al.  Site-specific Labelling with a Metal Chelator for Protein-structure Refinement , 2004, Journal of biomolecular NMR.

[17]  J H Prestegard,et al.  NMR structures of biomolecules using field oriented media and residual dipolar couplings , 2000, Quarterly Reviews of Biophysics.

[18]  L. Kay,et al.  Nuclear magnetic resonance spectroscopy of high-molecular-weight proteins. , 2004, Annual review of biochemistry.

[19]  J. Bowie,et al.  A method for assessing the stability of a membrane protein. , 1997, Biochemistry.

[20]  A. Gunasekera,et al.  Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex. , 2005, Biochemistry.

[21]  Backbone resonance assignment in large protonated proteins using a combination of new 3D TROSY-HN(CA)HA, 4D TROSY-HACANH and 13C-detected HACACO experiments , 2003, Journal of biomolecular NMR.

[22]  Gianluigi Veglia,et al.  Serine 16 phosphorylation induces an order-to-disorder transition in monomeric phospholamban. , 2005, Biochemistry.

[23]  Janet L. Smith,et al.  A defined protein–detergent–lipid complex for crystallization of integral membrane proteins: The cytochrome b6f complex of oxygenic photosynthesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Klein-Seetharaman,et al.  Solution 19F nuclear Overhauser effects in structural studies of the cytoplasmic domain of mammalian rhodopsin , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  T. Sawasaki,et al.  High-throughput, genome-scale protein production method based on the wheat germ cell-free expression system , 2004, Journal of Structural and Functional Genomics.

[26]  T. Ikegami,et al.  Conformation of a peptide ligand bound to its G-protein coupled receptor , 2001, Nature Structural Biology.

[27]  R. H. Fillingame,et al.  Structural model of the transmembrane Fo rotary sector of H+-transporting ATP synthase derived by solution NMR and intersubunit cross-linking in situ. , 2002, Biochimica et biophysica acta.

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

[29]  J. Weigelt Single Scan, Sensitivity- and Gradient-Enhanced TROSY for Multidimensional NMR Experiments , 1998 .

[30]  Wing-Yiu Choy,et al.  Solution structure and dynamics of the outer membrane enzyme PagP by NMR , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  E. Dennis,et al.  Interfacial properties and critical micelle concentration of lysophospholipids. , 1989, Biochemistry.

[32]  S. White,et al.  Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. II. Distribution and packing of terminal methyl groups. , 1992, Biophysical journal.

[33]  F. Separovic,et al.  Solid‐state NMR Structure Determination , 2003, IUBMB life.

[34]  C. Sanders,et al.  Oxygen as a paramagnetic probe of membrane protein structure by cysteine mutagenesis and (19)F NMR spectroscopy. , 2002, Journal of the American Chemical Society.

[35]  L. Kay,et al.  Solution structure and dynamics of integral membrane proteins by NMR: a case study involving the enzyme PagP. , 2005, Methods in enzymology.

[36]  Alexander Eletsky,et al.  A novel strategy for the assignment of side-chain resonances in completely deuterated large proteins using 13C spectroscopy , 2003, Journal of biomolecular NMR.

[37]  J. Popot,et al.  NMR study of a membrane protein in detergent-free aqueous solution. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  T. Cross Solid-state nuclear magnetic resonance characterization of gramicidin channel structure. , 1997, Methods in enzymology.

[39]  B. Sykes,et al.  Methods to study membrane protein structure in solution. , 1994, Methods in enzymology.

[40]  Konstantin Pervushin,et al.  Simultaneous 1H- or 2H-, 15N- and multiple-band-selective 13C-decoupling during acquisition in 13C-detected experiments with proteins and oligonucleotides , 2005, Journal of biomolecular NMR.

[41]  H. Weltzien,et al.  Quantitative studies on lysolecithin-mediated hemolysis. Use of ether-deoxy lysolecithin analogs with varying aliphatic chain-lengths. , 1977, Biochimica et biophysica acta.

[42]  L. Kay,et al.  Line narrowing in methyl-TROSY using zero-quantum 1H-13C NMR spectroscopy. , 2004, Journal of the American Chemical Society.

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

[44]  J. Becker,et al.  Synthetic peptides as probes for conformational preferences of domains of membrane receptors , 2005, Biopolymers.

[45]  J. Klein-Seetharaman,et al.  Solution NMR spectroscopy of [α-15N]lysine-labeled rhodopsin: The single peak observed in both conventional and TROSY-type HSQC spectra is ascribed to Lys-339 in the carboxyl-terminal peptide sequence , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Girvin,et al.  Determination of local protein structure by spin label difference 2D NMR: the region neighboring Asp61 of subunit c of the F1F0 ATP synthase. , 1994, Biochemistry.

[47]  C. Sanders,et al.  Bicelles: a model membrane system for all seasons? , 1998, Structure.

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

[49]  Masasuke Yoshida,et al.  Conformational change of H+-ATPase beta monomer revealed on segmental isotope labeling NMR spectroscopy. , 2004, Journal of the American Chemical Society.

[50]  S. Züger,et al.  Intein-based biosynthetic incorporation of unlabeled protein tags into isotopically labeled proteins for NMR studies , 2005, Nature Biotechnology.

[51]  J. Hus,et al.  De novo determination of protein structure by NMR using orientational and long-range order restraints. , 2000, Journal of molecular biology.

[52]  E. Gouaux,et al.  Probing the folding and unfolding of wild-type and mutant forms of bacteriorhodopsin in micellar solutions: evaluation of reversible unfolding conditions. , 1999, Biochemistry.

[53]  Steven O. Smith,et al.  Transmembrane interactions in the activation of the Neu receptor tyrosine kinase. , 2002, Biochemistry.

[54]  S. Grzesiek,et al.  Solution NMR of proteins within polyacrylamide gels: Diffusional properties and residual alignment by mechanical stress or embedding of oriented purple membranes , 2000, Journal of biomolecular NMR.

[55]  M. Girvin,et al.  Structural changes linked to proton translocation by subunit c of the ATP synthase , 1999, Nature.

[56]  J. Klein-Seetharaman,et al.  NMR spectroscopy in studies of light-induced structural changes in mammalian rhodopsin: applicability of solution (19)F NMR. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[57]  S. White,et al.  Membrane protein folding and stability: physical principles. , 1999, Annual review of biophysics and biomolecular structure.

[58]  K. Pervushin,et al.  Improved TROSY-HNCA experiment with suppression of conformational exchange induced relaxation , 2001, Journal of biomolecular NMR.

[59]  R. MacKinnon,et al.  Semisynthesis and folding of the potassium channel KcsA. , 2002, Journal of the American Chemical Society.

[60]  L. Thompson Solid-state NMR studies of the structure and mechanisms of proteins. , 2002, Current opinion in structural biology.

[61]  A. Makriyannis,et al.  The conformation of the cytoplasmic helix 8 of the CB1 cannabinoid receptor using NMR and circular dichroism. , 2005, Biochimica et biophysica acta.

[62]  Sow-Hsin Chen,et al.  Small-angle neutron scattering techniques applied to the study of polydisperse rodlike diheptanoylphosphatidylcholine micelles , 1987 .

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

[64]  Effects of anionic lipid and ion concentrations on the topology and segmental mobility of colicin Ia channel domain from solid-state NMR. , 2006, Biochemistry.

[65]  D. Otzen Folding of DsbB in mixed micelles: a kinetic analysis of the stability of a bacterial membrane protein. , 2003, Journal of molecular biology.

[66]  J. Bowie,et al.  How to Prepare Membrane Proteins for Solid‐State NMR: A Case Study on the α‐Helical Integral Membrane Protein Diacylglycerol Kinase from E. coli , 2005, Chembiochem : a European journal of chemical biology.

[67]  Charles R Sanders,et al.  Disease-related misassembly of membrane proteins. , 2004, Annual review of biophysics and biomolecular structure.

[68]  W. Dowhan,et al.  Molecular basis for membrane phospholipid diversity: why are there so many lipids? , 1997, Annual review of biochemistry.

[69]  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.

[70]  M. Girvin,et al.  An evaluation of detergents for NMR structural studies of membrane proteins , 2004, Journal of biomolecular NMR.

[71]  Alexander Shekhtman,et al.  Semisynthesis of a segmental isotopically labeled protein splicing precursor: NMR evidence for an unusual peptide bond at the N-extein-intein junction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[72]  D. Marsh,et al.  The protein-lipid interface: perspectives from magnetic resonance and crystal structures. , 2004, Biochimica et biophysica acta.

[73]  N. Go,et al.  Refined structure of melittin bound to perdeuterated dodeclylphoscholine micelles as studied by 2D‐NMR and distance geometry calculation , 1991, Proteins.

[74]  S. Opella,et al.  Rotational diffusion of membrane proteins in aligned phospholipid bilayers by solid-state NMR spectroscopy. , 2006, Journal of magnetic resonance.

[75]  G. Wagner,et al.  Utilization of site-directed spin labeling and high-resolution heteronuclear nuclear magnetic resonance for global fold determination of large proteins with limited nuclear overhauser effect data. , 2000, Biochemistry.

[76]  Y. Ishii,et al.  Controlling residual dipolar couplings in high-resolution NMR of proteins by strain induced alignment in a gel , 2001, Journal of biomolecular NMR.

[77]  G. Wider,et al.  Membrane Protein–Lipid Interactions in Mixed Micelles Studied by NMR Spectroscopy with the Use of Paramagnetic Reagents , 2004, Chembiochem : a European journal of chemical biology.

[78]  E. Dennis,et al.  Solubilization of phospholipids by detergents. Structural and kinetic aspects. , 1983, Biochimica et biophysica acta.

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

[80]  K. Wüthrich,et al.  Physicochemical studies of the protein-lipid interactions in melittin-containing micelles. , 1979, Biochimica et biophysica acta.

[81]  T. Cierpicki,et al.  Charged gels as orienting media for measurement of residual dipolar couplings in soluble and integral membrane proteins. , 2004, Journal of the American Chemical Society.

[82]  Volker Dötsch,et al.  Efficient strategy for the rapid backbone assignment of membrane proteins. , 2005, Journal of the American Chemical Society.

[83]  D. Nietlispach Suppression of anti-TROSY lines in a sensitivity enhanced gradient selection TROSY scheme , 2005, Journal of biomolecular NMR.

[84]  Wing-Yiu Choy,et al.  Solution NMR-derived global fold of a monomeric 82-kDa enzyme. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[85]  1H-15N backbone resonance assignments of bacteriorhodopsin. , 1996, Pharmaceutica acta Helvetiae.

[86]  L. Kay,et al.  Structure and dynamics of bacteriophage IKe major coat protein in MPG micelles by solution NMR. , 1996, Biochemistry.

[87]  C. Sanders,et al.  Escherichia coli diacylglycerol kinase: a case study in the application of solution NMR methods to an integral membrane protein. , 1997, Biophysical journal.

[88]  G. Privé,et al.  Lipopeptide detergents designed for the structural study of membrane proteins , 2003, Nature Biotechnology.

[89]  C. Schwarz,et al.  NMR investigation of the multidrug transporter EmrE, an integral membrane protein. , 1998, European journal of biochemistry.

[90]  A. Bax,et al.  Micelle-induced curvature in a water-insoluble HIV-1 Env peptide revealed by NMR dipolar coupling measurement in stretched polyacrylamide gel. , 2002, Journal of the American Chemical Society.

[91]  Matthias Müller,et al.  Development of a Minimal Cell‐Free Translation System for the Synthesis of Presecretory and Integral Membrane Proteins , 2008, Biotechnology progress.

[92]  Alan S. Stern,et al.  Optimization of 13C direct detection NMR methods , 2004, Journal of biomolecular NMR.

[93]  A. Bax Weak alignment offers new NMR opportunities to study protein structure and dynamics , 2003, Protein science : a publication of the Protein Society.

[94]  A. Bax,et al.  Measurement of Three-bond, 13C′-13Cβ J Couplings in Human Ubiquitin by a Triple Resonance, E. COSY-type NMR Technique , 1998, Journal of biomolecular NMR.

[95]  C. Sanders,et al.  Customizing model membranes and samples for NMR spectroscopic studies of complex membrane proteins. , 2000, Biochimica et biophysica acta.

[96]  C. Cass,et al.  Glucose and nucleoside transporters of human erythrocytes: effects of detergents on immunoadsorption of a membrane protein to its monoclonal antibody. , 1991, Biochimica et biophysica acta.

[97]  Lukas K. Tamm,et al.  Structure of outer membrane protein A transmembrane domain by NMR spectroscopy , 2001, Nature Structural Biology.

[98]  Mapping the oligomeric interface of diacylglycerol kinase by engineered thiol cross-linking: homologous sites in the transmembrane domain. , 2000, Biochemistry.

[99]  T. Kigawa,et al.  Expression of G protein coupled receptors in a cell-free translational system using detergents and thioredoxin-fusion vectors. , 2005, Protein expression and purification.

[100]  Yan Xu,et al.  Structure and dynamics of the second and third transmembrane domains of human glycine receptor. , 2005, Biochemistry.

[101]  J. Rosenbusch The critical role of detergents in the crystallization of membrane proteins. , 1990, Journal of structural biology.

[102]  C. Richter,et al.  Carbon‐Detected NMR Experiments To Investigate Structure and Dynamics of Biological Macromolecules , 2001, Chembiochem : a European journal of chemical biology.

[103]  S. Grzesiek,et al.  Charged acrylamide copolymer gels as media for weak alignment , 2002, Journal of biomolecular NMR.

[104]  Charles R Sanders,et al.  French Swimwear for Membrane Proteins , 2004, Chembiochem : a European journal of chemical biology.

[105]  C. Carlin,et al.  A Structural Model for the Membrane-bound Form of the Juxtamembrane Domain of the Epidermal Growth Factor Receptor* , 2005, Journal of Biological Chemistry.

[106]  C. Yu,et al.  Amyloid-like Fibril Formation in an All β-Barrel Protein Involves the Formation of Partially Structured Intermediate(s)* , 2002, The Journal of Biological Chemistry.

[107]  C. Sanders,et al.  On choosing a detergent for solution NMR studies of membrane proteins , 1998, Journal of biomolecular NMR.

[108]  K. Wüthrich,et al.  High resolution nuclear magnetic resonance studies of the conformation and orientation of melittin bound to a lipid-water interface. , 1982, Biophysical journal.

[109]  L. Kay,et al.  Stereospecific NMR assignments of prochiral methyls, rotameric states and dynamics of valine residues in malate synthase G. , 2004, Journal of the American Chemical Society.

[110]  James H. Prestegard,et al.  A Transmembrane Helix Dimer: Structure and Implications , 1997, Science.

[111]  A. Bax,et al.  Measurement of three-bond nitrogen-carbon J couplings in proteins uniformly enriched in nitrogen-15 and carbon-13 , 1993 .

[112]  M. Baldus,et al.  High-resolution solid-state NMR applied to polypeptides and membrane proteins. , 2003, Accounts of chemical research.

[113]  D. Engelman,et al.  Detergents modulate dimerization, but not helicity, of the glycophorin A transmembrane domain. , 1999, Journal of molecular biology.

[114]  Y. Kyōgoku,et al.  NMR observation of selected segments in a larger protein: central-segment isotope labeling through intein-mediated ligation. , 1999, Biochemistry.

[115]  J. Bushweller,et al.  Structure, dynamics and function of the outer membrane protein A (OmpA) and influenza hemagglutinin fusion domain in detergent micelles by solution NMR , 2003, FEBS letters.

[116]  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.

[117]  L. Kay,et al.  The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics of proteins. , 1998, Annual review of biophysics and biomolecular structure.

[118]  N. Nielsen,et al.  Techniques and applications of NMR to membrane proteins (Review) , 2004 .

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

[120]  Laurent Verdier,et al.  Novel Techniques for Weak Alignment of Proteins in Solution Using Chemical Tags Coordinating Lanthanide Ions , 2004, Journal of biomolecular NMR.

[121]  G. Wider,et al.  NMR structure of the integral membrane protein OmpX. , 2004, Journal of molecular biology.

[122]  J. P. Walsh,et al.  sn-1,2-Diacylglycerol kinase of Escherichia coli. Mixed micellar analysis of the phospholipid cofactor requirement and divalent cation dependence. , 1986, The Journal of biological chemistry.

[123]  C. Aisenbrey,et al.  The alignment, structure and dynamics of membrane-associated polypeptides by solid-state NMR spectroscopy. , 2004, Biochimica et biophysica acta.

[124]  R. Riek,et al.  Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[125]  David S. Cafiso,et al.  Identifying conformational changes with site-directed spin labeling , 2000, Nature Structural Biology.

[126]  S. Krishnaswamy,et al.  Overexpression, refolding, and purification of the major immunodominant outer membrane porin OmpC from Salmonella typhi: characterization of refolded OmpC. , 2005, Protein expression and purification.

[127]  Kurt Wüthrich,et al.  Lipid–protein interactions in DHPC micelles containing the integral membrane protein OmpX investigated by NMR spectroscopy , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[128]  Kurt Wüthrich,et al.  NMR solution structure determination of membrane proteins reconstituted in detergent micelles , 2003, FEBS letters.

[129]  S. Opella,et al.  Experimental nuclear magnetic resonance studies of membrane proteins. , 1994, Methods in enzymology.

[130]  A. Wand,et al.  Preparation, characterization, and NMR spectroscopy of encapsulated proteins dissolved in low viscosity fluids , 2003, Journal of biomolecular NMR.

[131]  Shigeyuki Yokoyama,et al.  Conformation of ligands bound to the muscarinic acetylcholine receptor. , 2002, Molecular pharmacology.

[132]  Sow-Hsin Chen,et al.  The use of small-angle neutron scattering to determine the structure and interaction of dihexanoylphosphatidylcholine micelles , 1986 .

[133]  V. Gaponenko,et al.  Breaking symmetry in the structure determination of (large) symmetric protein dimers , 2002, Journal of biomolecular NMR.

[134]  P. Yeagle,et al.  Structural studies on rhodopsin. , 2002, Biochimica et biophysica acta.

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

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

[137]  C. Sanders,et al.  An approximate model and empirical energy function for solute interactions with a water-phosphatidylcholine interface. , 1993, Biophysical journal.

[138]  D. Nebert,et al.  Sulfobetaine derivatives of bile acids: nondenaturing surfactants for membrane biochemistry. , 1983, Analytical biochemistry.

[139]  K. Pervushin The use of TROSY for detection and suppression of conformational exchange NMR line broadening in biological macromolecules , 2001, Journal of biomolecular NMR.

[140]  T. Torizawa,et al.  Efficient production of isotopically labeled proteins by cell-free synthesis: A practical protocol , 2004, Journal of biomolecular NMR.

[141]  Ad Bax,et al.  Evaluation of backbone proton positions and dynamics in a small protein by liquid crystal NMR spectroscopy. , 2003, Journal of the American Chemical Society.

[142]  A. Bax,et al.  Determination of φ and χ1 Angles in Proteins from 13C−13C Three-Bond J Couplings Measured by Three-Dimensional Heteronuclear NMR. How Planar Is the Peptide Bond? , 1997 .

[143]  A. Wand,et al.  New reverse micelle surfactant systems optimized for high-resolution NMR spectroscopy of encapsulated proteins. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[144]  L. Kay,et al.  Structural characterization of proteins with an attached ATCUN motif by paramagnetic relaxation enhancement NMR spectroscopy. , 2001, Journal of the American Chemical Society.

[145]  Lan Guan,et al.  An approach to membrane protein structure without crystals , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[146]  M. Kainosho,et al.  Localisation of methionine residues in bacteriorhodopsin by carbonyl 13C‐NMR with sequence‐specific assignments , 1993, FEBS letters.

[147]  S. Opella,et al.  Weak alignment of membrane proteins in stressed polyacrylamide gels. , 2004, Journal of magnetic resonance.

[148]  D. Nolde,et al.  Three-dimensional structure of proteolytic fragment 163-231 of bacterioopsin determined from nuclear magnetic resonance data in solution. , 1992, European journal of biochemistry.

[149]  S. So,et al.  NMR structure of the thromboxane A2 receptor ligand recognition pocket. , 2004, European journal of biochemistry.

[150]  D. Cafiso,et al.  Spectroscopic evidence that osmolytes used in crystallization buffers inhibit a conformation change in a membrane protein. , 2003, Biochemistry.

[151]  L. Kay,et al.  Methyl Groups as Probes of Structure and Dynamics in NMR Studies of High‐Molecular‐Weight Proteins , 2005, Chembiochem : a European journal of chemical biology.

[152]  L. Kay,et al.  New developments in isotope labeling strategies for protein solution NMR spectroscopy. , 2000, Current opinion in structural biology.

[153]  R. Leatherbarrow,et al.  Effect of osmolytes on the exchange rates of backbone amide protons in proteins. , 1998, Biochemistry.

[154]  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.

[155]  J. P. Walsh,et al.  sn-1,2-Diacylglycerol kinase of Escherichia coli. Structural and kinetic analysis of the lipid cofactor dependence. , 1986, Journal of Biological Chemistry.

[156]  Heinz Rüterjans,et al.  High level cell-free expression and specific labeling of integral membrane proteins. , 2004, European journal of biochemistry.

[157]  I. Bertini,et al.  Paramagnetic probes in metalloproteins. , 2001, Methods in enzymology.

[158]  D. Engelman,et al.  Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles. , 1983, Journal of molecular biology.

[159]  A. Bax,et al.  Relaxation-optimized NMR spectroscopy of methylene groups in proteins and nucleic acids. , 2004, Journal of the American Chemical Society.

[160]  Che Ma,et al.  Lanthanide ions bind specifically to an added "EF-hand" and orient a membrane protein in micelles for solution NMR spectroscopy. , 2000, Journal of magnetic resonance.

[161]  A. Bax,et al.  Structure and orientation of a G protein fragment in the receptor bound state from residual dipolar couplings. , 2002, Journal of molecular biology.

[162]  C. Sanders,et al.  Membrane protein preparation for TROSY NMR screening. , 2005, Methods in enzymology.

[163]  J. Chou,et al.  The structure of phospholamban pentamer reveals a channel-like architecture in membranes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[164]  Walid A Houry,et al.  Quantitative NMR spectroscopy of supramolecular complexes: dynamic side pores in ClpP are important for product release. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[165]  H. Hauser Short-chain phospholipids as detergents. , 2000, Biochimica et biophysica acta.

[166]  A. I. Popov,et al.  Three-dimensional structure of (1-71)bacterioopsin solubilized in methanol/chloroform and SDS micelles determined by 15N-1H heteronuclear NMR spectroscopy. , 1994, European journal of biochemistry.

[167]  M. Girvin,et al.  Solution structure of the transmembrane H+-transporting subunit c of the F1F0 ATP synthase. , 1998, Biochemistry.

[168]  G. Wider,et al.  TROSY in NMR studies of the structure and function of large biological macromolecules. , 2003, Current opinion in structural biology.

[169]  D. Engelman,et al.  Amphipols: polymeric surfactants for membrane biology research , 2003, Cellular and Molecular Life Sciences CMLS.

[170]  F. Kukita,et al.  Interaction stabilizing tertiary structure of bacteriorhodopsin studied by denaturation experiments , 1995, Proteins.

[171]  Volker Dötsch,et al.  Evaluation of detergents for the soluble expression of α‐helical and β‐barrel‐type integral membrane proteins by a preparative scale individual cell‐free expression system , 2005 .

[172]  Haruki Nakamura,et al.  Structural basis of the KcsA K(+) channel and agitoxin2 pore-blocking toxin interaction by using the transferred cross-saturation method. , 2003, Structure.