Elucidation of the protein folding landscape by NMR.

NMR is one of the few experimental methods that can provide detailed insights into the structure and dynamics of unfolded and partly folded states of proteins. Mapping the protein folding landscape is of central importance to understanding the mechanism of protein folding. In addition, it is now recognized that many proteins are intrinsically unstructured in their functional states, while partly folded states of several cellular proteins have been implicated in amyloid disease. NMR is uniquely suited to characterize the structures present in the conformational ensemble and probe the dynamics of the polypeptide chain in unfolded and partially folded protein states.

[1]  T. Konno,et al.  Pressure-dissociable reversible assembly of intrinsically denatured lysozyme is a precursor for amyloid fibrils , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J R Tolman,et al.  Dipolar couplings as a probe of molecular dynamics and structure in solution. , 2001, Current opinion in structural biology.

[3]  Kazuyuki Akasaka,et al.  Close identity of a pressure-stabilized intermediate with a kinetic intermediate in protein folding , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[4]  L. Kay,et al.  Probing slow time scale dynamics at methyl-containing side chains in proteins by relaxation dispersion NMR measurements: application to methionine residues in a cavity mutant of T4 lysozyme. , 2001, Journal of the American Chemical Society.

[5]  C. Dobson,et al.  Kinetic studies of protein folding using NMR spectroscopy , 1998, Nature Structural Biology.

[6]  Arto Annila,et al.  On the origin of residual dipolar couplings from denatured proteins. , 2003, Journal of the American Chemical Society.

[7]  F. Gurd,et al.  Carbon 13 nuclear magnetic resonance of pentapeptides of glycine containing central residues of serine, threonine, aspartic and glutamic acids, asparagine, and glutamine. , 1973, The Journal of biological chemistry.

[8]  Lorna J. Smith,et al.  Toward a Description of the Conformations of Denatured States of Proteins. Comparison of a Random Coil Model with NMR Measurements , 1996 .

[9]  L. Kay,et al.  Deuterium spin probes of side-chain dynamics in proteins. 1. Measurement of five relaxation rates per deuteron in (13)C-labeled and fractionally (2)H-enriched proteins in solution. , 2002, Journal of the American Chemical Society.

[10]  L. Kay,et al.  Probing Residual Interactions in Unfolded Protein States Using NMR Spin Relaxation Techniques: An Application to Δ131Δ , 2003 .

[11]  F. Poulsen,et al.  Short-range, long-range and transition state interactions in the denatured state of ACBP from residual dipolar couplings. , 2004, Journal of molecular biology.

[12]  L. Kay,et al.  Measurement of slow (micros-ms) time scale dynamics in protein side chains by (15)N relaxation dispersion NMR spectroscopy: application to Asn and Gln residues in a cavity mutant of T4 lysozyme. , 2001, Journal of the American Chemical Society.

[13]  K. Plaxco,et al.  Toward a taxonomy of the denatured state: small angle scattering studies of unfolded proteins. , 2002, Advances in protein chemistry.

[14]  S. Radford,et al.  Protein folding mechanisms: new methods and emerging ideas. , 2000, Current opinion in structural biology.

[15]  H. Dyson,et al.  Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d , 2004, Nature Structural &Molecular Biology.

[16]  P E Wright,et al.  Nuclear magnetic resonance methods for elucidation of structure and dynamics in disordered states. , 2001, Methods in enzymology.

[17]  Hua Li,et al.  Pressure‐induced unfolding of the molten globule of all‐Ala α‐lactalbumin , 2003 .

[18]  P. Wright,et al.  ‘Random coil’ 1H chemical shifts obtained as a function of temperature and trifluoroethanol concentration for the peptide series GGXGG , 1995, Journal of biomolecular NMR.

[19]  D. Shortle,et al.  Characterization of long-range structure in the denatured state of staphylococcal nuclease. II. Distance restraints from paramagnetic relaxation and calculation of an ensemble of structures. , 1997, Journal of molecular biology.

[20]  E. Elson,et al.  What fluorescence correlation spectroscopy can tell us about unfolded proteins. , 2002, Advances in protein chemistry.

[21]  H. Kalbitzer,et al.  1H-NMR parameters of common amino acid residues measured in aqueous solutions of the linear tetrapeptides Gly-Gly-X-Ala at pressures between 0.1 and 200 MPa. , 2002, Biophysical chemistry.

[22]  Jonathan A. Jones,et al.  TWO-DIMENSIONAL 15N-1H PHOTO-CIDNP AS A SURFACE PROBE OF NATIVE AND PARTIALLY STRUCTURED PROTEINS , 1999 .

[23]  G. Lipari.  Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules , 1982 .

[24]  Dyson Hj,et al.  [12] - Nuclear Magnetic Resonance Methods for Elucidation of Structure and Dynamics in Disordered States , 2001 .

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

[26]  Andrew L. Lee,et al.  Direct Demonstration of Structural Similarity between Native and Denatured Eglin C † , 2004 .

[27]  H. Dyson,et al.  Unfolded proteins and protein folding studied by NMR. , 2004, Chemical reviews.

[28]  Christopher M. Dobson,et al.  The effects of guanidine hydrochloride on the ’random coil‘ conformations and NMR chemical shifts of the peptide series GGXGG , 1997, Journal of biomolecular NMR.

[29]  Gerard J A Kroon,et al.  Structural characterization of unfolded states of apomyoglobin using residual dipolar couplings. , 2004, Journal of molecular biology.

[30]  G. Rose,et al.  Hydrophobicity of amino acid residues in globular proteins. , 1985, Science.

[31]  L. Kay,et al.  A study of protein side-chain dynamics from new 2H auto-correlation and 13C cross-correlation NMR experiments: application to the N-terminal SH3 domain from drk. , 1998, Journal of molecular biology.

[32]  L. Kay,et al.  Comprehensive NOE characterization of a partially folded large fragment of staphylococcal nuclease Delta131Delta, using NMR methods with improved resolution. , 1997, Journal of molecular biology.

[33]  C. Dobson,et al.  Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR , 2004, Nature.

[34]  P. Lu,et al.  Residual dipolar couplings in nucleic acid structure determination. , 2002, Current opinion in structural biology.

[35]  F. Bermejo,et al.  A study of the NH NMR signals of Gly-Gly-X-Ala tetrapeptides in H2O at low temperature. , 1986 .

[36]  S. Prusiner,et al.  Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc? , 2002, Biochemistry.

[37]  C M Dobson,et al.  Protein Folding Monitored at Individual Residues During a Two-Dimensional NMR Experiment , 1996, Science.

[38]  Establishing a degree of order: obtaining high-resolution NMR structures from molecular alignment. , 1999, Structure.

[39]  D. Shortle,et al.  Backbone dynamics of a highly disordered 131 residue fragment of staphylococcal nuclease. , 1994, Journal of molecular biology.

[40]  N. S. Bhavesh,et al.  An efficient high-throughput resonance assignment procedure for structural genomics and protein folding research by NMR. , 2001, Biochemistry.

[41]  C. Dobson.  Protein folding and misfolding , 2003, Nature.

[42]  Y. Ishii,et al.  Alignment of Biopolymers in Strained Gels: A New Way To Create Detectable Dipole−Dipole Couplings in High-Resolution Biomolecular NMR , 2000 .

[43]  Christopher M. Dobson,et al.  Following protein folding in real time using NMR spectroscopy , 1995, Nature Structural Biology.

[44]  P E Wright,et al.  Sequence-dependent correction of random coil NMR chemical shifts. , 2001, Journal of the American Chemical Society.

[45]  C. Dobson,et al.  Rapid formation of non-native contacts during the folding of HPr revealed by real-time photo-CIDNP NMR and stopped-flow fluorescence experiments. , 2003, Journal of molecular biology.

[46]  J H Prestegard,et al.  Nuclear magnetic dipole interactions in field-oriented proteins: information for structure determination in solution. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[47]  H. Dyson,et al.  NMR structural and dynamic characterization of the acid-unfolded state of apomyoglobin provides insights into the early events in protein folding. , 2001, Biochemistry.

[48]  F. Gurd,et al.  Carbon 13 nuclear magnetic resonance of pentapeptides of glycine containing central residues of methionine, proline, arginine, and lysine. , 1974, The Journal of biological chemistry.

[49]  J. Onuchic,et al.  Toward an outline of the topography of a realistic protein-folding funnel. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[50]  A. Gronenborn,et al.  Measurement of Residual Dipolar Couplings of Macromolecules Aligned in the Nematic Phase of a Colloidal Suspension of Rod-Shaped Viruses , 1998 .

[51]  P. Wright,et al.  Measurement of relaxation time constants for methyl groups by proton-detected heteronuclear NMR spectroscopy , 1991 .

[52]  J. Prestegard,et al.  New techniques in structural NMR — anisotropic interactions , 1998, Nature Structural Biology.

[53]  K. Akasaka.  Highly fluctuating protein structures revealed by variable-pressure nuclear magnetic resonance. , 2003, Biochemistry.

[54]  H. Jane Dyson,et al.  Random coil chemical shifts in acidic 8 M urea: Implementation of random coil shift data in NMRView , 2000, Journal of biomolecular NMR.

[55]  D. Shortle,et al.  Persistence of Native-Like Topology in a Denatured Protein in 8 M Urea , 2001, Science.

[56]  K. Wüthrich,et al.  Carbon‐13 NMR chemical shifts of the common amino acid residues measured in aqueous solutions of the linear tetrapeptides H‐Gly‐Gly‐ X‐L‐ Ala‐OH , 1978 .

[57]  C D Kroenke,et al.  Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond motions in biological macromolecules. , 2001, Methods in enzymology.

[58]  L. Kay,et al.  Dynamics of methyl groups in proteins as studied by proton-detected 13C NMR spectroscopy. Application to the leucine residues of staphylococcal nuclease. , 1992, Biochemistry.

[59]  F. Gurd,et al.  Carbon 13 nuclear magnetic resonance of pentapeptides of glycine containing central residues of aliphatic amino acids. , 1973, The Journal of biological chemistry.

[60]  L. Kay,et al.  Side chain dynamics in unfolded protein states: an NMR based 2H spin relaxation study of delta131delta. , 2003, Journal of the American Chemical Society.

[61]  D. Shortle,et al.  Characterization of long-range structure in the denatured state of staphylococcal nuclease. I. Paramagnetic relaxation enhancement by nitroxide spin labels. , 1997, Journal of molecular biology.

[62]  P E Wright,et al.  Native and non-native secondary structure and dynamics in the pH 4 intermediate of apomyoglobin. , 2000, Biochemistry.

[63]  L. Kay,et al.  Slow internal dynamics in proteins: application of NMR relaxation dispersion spectroscopy to methyl groups in a cavity mutant of T4 lysozyme. , 2002, Journal of the American Chemical Society.

[64]  Lorna J. Smith,et al.  Understanding protein folding via free-energy surfaces from theory and experiment. , 2000, Trends in biochemical sciences.

[65]  L. Kay,et al.  Side chain dynamics in unfolded protein states: an NMR based 2H spin relaxation study of Δ131Δ , 2003 .

[66]  T. Keiderling,et al.  Unfolded peptides and proteins studied with infrared absorption and vibrational circular dichroism spectra. , 2002, Advances in protein chemistry.

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

[68]  J. Udgaonkar,et al.  NMR studies of protein folding , 2003 .

[69]  O. Jardetzky,et al.  Investigation of the neighboring residue effects on protein chemical shifts. , 2002, Journal of the American Chemical Society.

[70]  J H Prestegard,et al.  Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings. , 2000, Journal of magnetic resonance.

[71]  M. Karplus,et al.  Three key residues form a critical contact network in a protein folding transition state , 2001, Nature.

[72]  H. Dyson,et al.  Chemical shift dispersion and secondary structure prediction in unfolded and partly folded proteins , 1997, FEBS letters.

[73]  J. Onuchic,et al.  Funnels, pathways, and the energy landscape of protein folding: A synthesis , 1994, Proteins.

[74]  Y. Ando,et al.  Decreased thermodynamic stability as a crucial factor for familial amyloidotic polyneuropathy. , 2002, Journal of molecular biology.

[75]  Jeffrey W. Peng,et al.  Mapping of Spectral Density Functions Using Heteronuclear NMR Relaxation Measurements , 1992 .

[76]  R. Hodges,et al.  1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects , 1995, Journal of biomolecular NMR.

[77]  K. Lumb,et al.  Random-coil chemical shifts of phosphorylated amino acids , 1999, Journal of biomolecular NMR.

[78]  H. Dyson,et al.  Coupling of folding and binding for unstructured proteins. , 2002, Current opinion in structural biology.

[79]  B. Brutscher.  Combined frequency- and time-domain NMR spectroscopy. Application to fast protein resonance assignment , 2004, Journal of biomolecular NMR.

[80]  Kazuyuki Akasaka,et al.  Pressure-dependent changes in the solution structure of hen egg-white lysozyme. , 2003, Journal of molecular biology.

[81]  Millisecond Time Resolved Photo-CIDNP NMR Reveals a Non-Native Folding Intermediate on the Ion-Induced Refolding Pathway of Bovine α-Lactalbumin. , 2001, Angewandte Chemie.

[82]  A. Szabó,et al.  Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity , 1982 .

[83]  H. Dyson,et al.  Insights into the structure and dynamics of unfolded proteins from nuclear magnetic resonance. , 2002, Advances in protein chemistry.

[84]  M. Reily,et al.  The 13C chemical shifts of amino acids in aqueous solution containing organic solvents: Application to the secondary structure characterization of peptides in aqueous trifluoroethanol solution , 1994, Journal of biomolecular NMR.

[85]  L. Serrano.  Comparison between the phi distribution of the amino acids in the protein database and NMR data indicates that amino acids have various phi propensities in the random coil conformation. , 1995, Journal of molecular biology.

[86]  D. Torchia,et al.  Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach , 2003, Journal of biomolecular NMR.

[87]  K. Akasaka.  Exploring the entire conformational space of proteins by high-pressure NMR , 2003 .

[88]  D. Shortle,et al.  Molecular alignment of denatured states of staphylococcal nuclease with strained polyacrylamide gels and surfactant liquid crystalline phases. , 2002, Biochemistry.

[89]  D. Lilley,et al.  Carbon-13-NMR of peptides and proteins , 1978 .

[90]  Brian D. Sykes,et al.  Measurement of 2H T1 and T1.rho. Relaxation Times in Uniformly 13C-Labeled and Fractionally 2H-Labeled Proteins in Solution , 1995 .

[91]  T. James,et al.  Slow conformational dynamics in the hamster prion protein. , 2004, Biochemistry.

[92]  L. Barron,et al.  Unfolded proteins studied by Raman optical activity. , 2002, Advances in protein chemistry.

[93]  C. Dobson,et al.  Main-chain dynamics of a partially folded protein: 15N NMR relaxation measurements of hen egg white lysozyme denatured in trifluoroethanol. , 1996, Journal of molecular biology.

[94]  I. Kuntz,et al.  Distance measurements in spin-labeled lysozyme. , 1984, Biochemistry.

[95]  A. Szabó,et al.  Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 2. Analysis of experimental results , 1982 .

[96]  I. Kuntz,et al.  Two-dimensional 1H NMR of three spin-labeled derivatives of bovine pancreatic trypsin inhibitor. , 1986, Biochemistry.

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

[98]  L. Kay,et al.  Spectral density function mapping using 15N relaxation data exclusively , 1995, Journal of biomolecular NMR.

[99]  C. Dobson,et al.  Detection of residue contacts in a protein folding intermediate. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[100]  Gerhard Wider,et al.  Sequence-Corrected 15N "Random Coil" Chemical Shifts , 1994 .

[101]  L. Kay,et al.  Slow dynamics in folded and unfolded states of an SH3 domain. , 2001, Journal of the American Chemical Society.

[102]  M. Inouye,et al.  Backbone dynamics of the natively unfolded pro-peptide of subtilisin by heteronuclear NMR relaxation studies , 2001, Journal of biomolecular NMR.

[103]  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.

[104]  Jonathan A. Jones,et al.  Rapid sample-mixing technique for transient NMR and photo-CIDNP spectroscopy: applications to real-time protein folding. , 2003, Journal of the American Chemical Society.

[105]  D. Case,et al.  Assessment of zinc finger orientations by residual dipolar coupling constants , 2000, Journal of biomolecular NMR.

[106]  Ad Bax,et al.  Overall structure and sugar dynamics of a DNA dodecamer from homo- and heteronuclear dipolar couplings and 31P chemical shift anisotropy , 2003, Journal of biomolecular NMR.

[107]  M. W. Lassalle,et al.  Pressure-induced unfolding of the molten globule of all-Ala alpha-lactalbumin. , 2003, Protein science : a publication of the Protein Society.

[108]  B D Sykes,et al.  1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects , 1995, Journal of biomolecular NMR.

[109]  H. Dyson,et al.  Mapping long-range contacts in a highly unfolded protein. , 2002, Journal of molecular biology.

[110]  H. Dyson,et al.  Molecular hinges in protein folding: the urea-denatured state of apomyoglobin. , 2002, Biochemistry.

[111]  Daiwen Yang,et al.  1H-13C DIPOLE-DIPOLE CROSS-CORRELATED SPIN RELAXATION AS A PROBE OF DYNAMICS IN UNFOLDED PROTEINS : APPLICATION TO THE DRKN SH3 DOMAIN , 1999 .

[112]  Kurt Wüthrich,et al.  1H‐nmr parameters of the common amino acid residues measured in aqueous solutions of the linear tetrapeptides H‐Gly‐Gly‐X‐L‐Ala‐OH , 1979 .

[113]  C. N. Reilley,et al.  Carbon-13 NMR studies of amino acids: Chemical shifts, protonation shifts, microscopic protonation behavior , 1980 .

[114]  P. Wright,et al.  High pressure NMR reveals that apomyoglobin is an equilibrium mixture from the native to the unfolded. , 2002, Journal of molecular biology.

[115]  L J Smith,et al.  Side-chains in native and random coil protein conformations. Analysis of NMR coupling constants and chi1 torsion angle preferences. , 1998, Journal of molecular biology.

[116]  T. Oas,et al.  Submillisecond folding of monomeric lambda repressor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Julie D. Forman-Kay,et al.  Triple-resonance NOESY-based experiments with improved spectral resolution: Applications to structural characterization of unfolded, partially folded and folded proteins , 1997, Journal of biomolecular NMR.