Biophysical approaches to membrane protein structure determination.

Recently, there have been several technical advances in the use of solution and solid-state NMR spectroscopy to determine the structures of membrane proteins. The structures of several isolated transmembrane (TM) helices and pairs of TM helices have been solved by solution NMR methods. Similarly, the complete folds of two TM beta-barrel proteins with molecular weights of 16 and 19 kDa have been determined by solution NMR in detergent micelles. Solution NMR has also provided a first glimpse at the dynamics of an integral membrane protein. Structures of individual TM helices have also been determined by solid-state NMR. A combination of NMR with site-directed spin-label electron paramagnetic resonance or Fourier transform IR spectroscopy allows one to assemble quite detailed protein structures in the membrane.

[1]  D. Mccormick.  Sequence the Human Genome , 1986, Bio/Technology.

[2]  R. H. Fillingame,et al.  Molecular Rotary Motors , 1999, Science.

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

[4]  H. Oschkinat,et al.  Sample optimization and identification of signal patterns of amino acid side chains in 2D RFDR spectra of the alpha-spectrin SH3 domain. , 2000, Journal of magnetic resonance.

[5]  S. Tatulian,et al.  Secondary structure, orientation, oligomerization, and lipid interactions of the transmembrane domain of influenza hemagglutinin. , 2000, Biochemistry.

[6]  G. Veglia,et al.  Lanthanide Ion Binding to Adventitious Sites Aligns Membrane Proteins in Micelles for Solution NMR Spectroscopy , 2000 .

[7]  L. Kay,et al.  Improved 1HN-detected triple resonance TROSY-based experiments , 1999, Journal of biomolecular NMR.

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

[9]  Randal R Ketchem,et al.  High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR. , 1993, Science.

[10]  G. Schulz,et al.  The structure of the outer membrane protein OmpX from Escherichia coli reveals possible mechanisms of virulence. , 1999, Structure.

[11]  H. D. de Groot.  Solid-state NMR spectroscopy applied to membrane proteins. , 2000, Current opinion in structural biology.

[12]  Ad Bax,et al.  Protein Structure Determination Using Molecular Fragment Replacement and NMR Dipolar Couplings , 2000 .

[13]  R. H. Fillingame,et al.  Structure of the Membrane Domain of Subunit b of the Escherichia coli F0F1 ATP Synthase* , 1999, The Journal of Biological Chemistry.

[14]  J. Wang,et al.  Transmembrane domain of M2 protein from influenza A virus studied by solid-state (15)N polarization inversion spin exchange at magic angle NMR. , 2000, Biophysical journal.

[15]  G. Wider,et al.  The 3D NOESY-[(1)H,(15)N,(1)H]-ZQ-TROSY NMR experiment with diagonal peak suppression. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[16]  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.

[17]  J. V. van Esch,et al.  Physical chemical studies of short-chain lecithin homologues. II. Micellar weights of dihexanoyl- and diheptanoyllecithin. , 1974, Biophysical chemistry.

[18]  J. Prestegard,et al.  Nuclear magnetic resonance characterization of the myristoylated, N-terminal fragment of ADP-ribosylation factor 1 in a magnetically oriented membrane array. , 1998, Biochemistry.

[19]  E. Perozo,et al.  Structural rearrangements underlying K+-channel activation gating. , 1999, Science.

[20]  D. Engelman,et al.  Membrane protein folding and oligomerization: the two-stage model. , 1990, Biochemistry.

[21]  Isaiah T. Arkin,et al.  Site-Directed Dichroism As a Method for Obtaining Rotational and Orientational Constraints for Oriented Polymers , 1997 .

[22]  A. Watts,et al.  Magic angle-oriented sample spinning (MAOSS): A new approach toward biomembrane studies. , 1998, Journal of magnetic resonance.

[23]  S. Tatulian,et al.  Infrared spectroscopy of proteins and peptides in lipid bilayers , 1997, Quarterly Reviews of Biophysics.

[24]  S. Opella,et al.  Three-dimensional solid-state NMR experiment that correlates the chemical shift and dipolar coupling frequencies of two heteronuclei. , 1995, Journal of magnetic resonance. Series B.

[25]  Chris Sander,et al.  Completeness in structural genomics , 2001, Nature Structural Biology.

[26]  Kurt Wüthrich,et al.  TROSY-TYPE TRIPLE-RESONANCE EXPERIMENTS FOR SEQUENTIAL NMR ASSIGNMENTS OF LARGE PROTEINS , 1999 .

[27]  Charles Tanford,et al.  The Hydrophobic Effect: Formation of Micelles and Biological Membranes , 1991 .

[28]  J. Becker,et al.  Structure and topology of a peptide segment of the 6th transmembrane domain of the Saccharomyces cerevisae alpha-factor receptor in phospholipid bilayers. , 2001, Biopolymers.

[29]  S. Opella,et al.  Three-dimensional 13C shift/1H-15N coupling/15N shift solid-state NMR correlation spectroscopy. , 1999, Journal of magnetic resonance.

[30]  F. Marassi.  A simple approach to membrane protein secondary structure and topology based on NMR spectroscopy. , 2001, Biophysical journal.

[31]  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.

[32]  G. Schulz,et al.  Structure of the outer membrane protein A transmembrane domain , 1998, Nature Structural Biology.

[33]  J. Denny,et al.  Helix tilt of the M2 transmembrane peptide from influenza A virus: an intrinsic property. , 2000, Journal of molecular biology.

[34]  J. Overbeek,et al.  Physical chemical studies of short-chain lecithin homologues. 3. Phase separation and light scattering studies on aqueous dioctanoyllecithin solutions. , 1974, Biophysical chemistry.

[35]  A G Leslie,et al.  Molecular architecture of the rotary motor in ATP synthase. , 1999, Science.

[36]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[37]  S. Opella,et al.  Complete resolution of the solid-state NMR spectrum of a uniformly 15N-labeled membrane protein in phospholipid bilayers. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[38]  G. Heijne,et al.  Genome‐wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms , 1998, Protein science : a publication of the Protein Society.

[39]  K Wüthrich,et al.  TROSY in triple-resonance experiments: new perspectives for sequential NMR assignment of large proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  M Montal,et al.  Correlation of the structural and functional domains in the membrane protein Vpu from HIV-1. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Che Ma,et al.  Nuclear magnetic resonance of membrane-associated peptides and proteins. , 2001, Methods in enzymology.

[42]  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.

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

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

[45]  J. Prestegard,et al.  Magnetically-oriented phospholipid micelles as a tool for the study of membrane-associated molecules , 1994 .

[46]  K. Wüthrich,et al.  [15N,1H]/[13C,1H]-TROSY for simultaneous detection of backbone 15N–1H, aromatic 13C–1H and side-chain 15N–1H2 correlations in large proteins , 2000, Journal of biomolecular NMR.

[47]  H. Oschkinat,et al.  Backbone and Side Chain 13 C and 15 N Resonance Assignments of the a-Spectrin SH 3 Domain by Magic Angle Spinning Solid State NMR at 17.6 Tesla. , 2001 .

[48]  J. Gesell,et al.  Structures of the M2 channel-lining segments from nicotinic acetylcholine and NMDA receptors by NMR spectroscopy , 1999, Nature Structural Biology.

[49]  H. D. Groot.  Solid-state NMR spectroscopy applied to membrane proteins , 2000 .

[50]  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.

[51]  J Wang,et al.  Imaging membrane protein helical wheels. , 2000, Journal of magnetic resonance.

[52]  F. Sönnichsen,et al.  Conformationally specific misfolding of an integral membrane protein. , 2001, Biochemistry.

[53]  S. Opella,et al.  A solid-state NMR index of helical membrane protein structure and topology. , 2000, Journal of magnetic resonance.

[54]  Lukas K. Tamm,et al.  Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin , 2001, Nature Structural Biology.

[55]  A. Kukol,et al.  vpu transmembrane peptide structure obtained by site-specific fourier transform infrared dichroism and global molecular dynamics searching. , 1999, Biophysical journal.

[56]  Randal R Ketchem,et al.  High-resolution polypeptide structure in a lamellar phase lipid environment from solid state NMR derived orientational constraints. , 1997, Structure.

[57]  Use of a new label, (13)==(18)O, in the determination of a structural model of phospholamban in a lipid bilayer. Spatial restraints resolve the ambiguity arising from interpretations of mutagenesis data. , 2000, Journal of molecular biology.

[58]  R. Fu,et al.  Solid-state nuclear magnetic resonance investigation of protein and polypeptide structure. , 1999, Annual review of biophysics and biomolecular structure.

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

[60]  L. Kay,et al.  A 4D TROSY-based pulse scheme for correlating 1HNi,15Ni,13Cαi,13C′i−1 chemical shifts in high molecular weight, 15N,13C, 2H labeled proteins , 1999, Journal of biomolecular NMR.

[61]  J. Overbeek,et al.  Physical chemical studies of short-chain lecithin homologues. I. Influence of the chain length of the fatty acid ester and of electrolytes on the critical micelle concentration. , 1974, Biophysical chemistry.

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

[63]  C. Sanders,et al.  NMR-Based amide hydrogen-deuterium exchange measurements for complex membrane proteins: development and critical evaluation. , 2000, Journal of magnetic resonance.

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

[65]  Daiwen Yang,et al.  TROSY Triple-Resonance Four-Dimensional NMR Spectroscopy of a 46 ns Tumbling Protein , 1999 .

[66]  A. Bax,et al.  Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium. , 1997, Science.

[67]  R. Brasseur,et al.  Orientation and effects of mastoparan X on phospholipid bicelles. , 2001, Biophysical journal.

[68]  D. Marsh.  Nonaxiality in infrared dichroic ratios of polytopic transmembrane proteins. , 1998, Biophysical journal.

[69]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[70]  G. Zhu,et al.  Gradient and sensitivity enhancement of 2D TROSY with water flip-back, 3D NOESY-TROSY and TOCSY-TROSY experiments , 1999, Journal of biomolecular NMR.

[71]  M. Wiener,et al.  Outer membrane protein A of E. coli folds into detergent micelles, but not in the presence of monomeric detergent , 1999, Protein science : a publication of the Protein Society.

[72]  S. O. Smith,et al.  Structure of the transmembrane dimer interface of glycophorin A in membrane bilayers. , 2001, Biochemistry.