NMR spectroscopy brings invisible protein states into focus

Nature Chemical Biology

Volumn 5, Issue 11, 2009, Pages 808-814

  Baldwin, Andrew J ^a   Kay, Lewis E ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME; LIGAND; PROTEIN;

BIOLOGICAL ACTIVITY; CATALYSIS; LIGAND BINDING; MOLECULAR RECOGNITION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN FOLDING; REVIEW;

EID: 70350348011     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.238     Document Type: Review

References (99)

1. Hammes, G.G. Mechanism of enzyme catalysis. Nature 204, 342-343 (1964).
2. Fersht, A.R. Structure and Mechanism in Protein Science (W.H. Freeman, New York, 1998).
3. Karplus, M. & Kuriyan, J. Molecular dynamics and protein function. Proc. Natl. Acad. Sci. USA 102, 6679-6685 (2005).
4. Perutz, M.F. & Mathews, F.S. An X-ray study of azide methaemoglobin. J. Mol. Biol. 21, 199-202 (1966).
5. Hvidt, A. & Linderstrom-Lang, K. Exchange of hydrogen atoms in insulin with deuterium atoms in aqueous solutions. Biochim. Biophys. Acta 14, 574-575 (1954).
6. Wüthrich, K. & Wagner, G. Internal motion in globular proteins. Trends Biochem. Sci. 3, 227-230 (1978).
7. Snyder, G.H., Rowan, R. III, Karplus, S. & Sykes, B.D. Complete tyrosine assignments in the high field 1H nuclear magnetic resonance spectrum of the bovine pancreatic trypsin inhibitor. Biochemistry 14, 3765-3777 (1975).
8. Campbell, I.D., Dobson, C.M. & Williams, R.J. Proton magnetic resonance studies of the tyrosine residues of hen lysozyme-assignment and detection of conformational mobility. Proc. R. Soc. Lond. B 189, 503-509 (1975).
9. Austin, R.H., Beeson, K.W., Eisenstein, L., Frauenfelder, H. & Gunsalus, I.C. Dynamics of ligand binding to myoglobin. Biochemistry 14, 5355-5373 (1975).
10. McCammon, J.A., Gelin, B.R. & Karplus, M. Dynamics of folded proteins. Nature 267, 585-590 (1977).
11. Tokuriki, N. & Tawfik, D.S. Protein dynamism and evolvability. Science 324, 203-207 (2009).
12. Bryngelson, J.D. & Wolynes, P.G. Spin glasses and the statistical mechanics of protein folding. Proc. Natl. Acad. Sci. USA 84, 7524-7528 (1987).
13. Chan, H.S. & Dill, K.A. Polymer principles in protein structure and stability. Annu. Rev. Biophys. Biophys. Chem. 20, 447-490 (1991).
14. Wolynes, P.G. Recent successes of the energy landscape theory of protein folding and function. Q. Rev. Biophys. 38, 405-410 (2005).
15. Hegler, J.A., Weinkam, P. & Wolynes, P.G. The spectrum of biomolecular states and motions. HFSP J. 2, 307-313 (2008).
16. Kay, L.E., Torchia, D.A. & Bax, A. Backbone dynamics of proteins as studied by 15N inverse detected heteronuclear NMR spectroscopy: application to staphylococcal nuclease. Biochemistry 28, 8972-8979 (1989).
17. Baber, J.L., Szabo, A. & Tjandra, N. Analysis of slow interdomain motion of macromolecules using NMR relaxation data. J. Am. Chem. Soc. 123, 3953-3959 (2001).
18. Rueda, M. et al. A consensus view of protein dynamics. Proc. Natl. Acad. Sci. USA 104, 796-801 (2007).
19. Dobson, C.M. & Karplus, M. Internal motion of proteins: nuclear magnetic resonance measurements and dynamic simulations. Methods Enzymol. 131, 362-389 (1986).
20. Peng, J.W. & Wagner, G. Investigation of protein motions via relaxation measurements. Methods Enzymol. 239, 563-596 (1994).
21. Palmer, A.G., Williams, J. & McDermott, A. Nuclear magnetic resonance studies of biopolymer dynamics. J. Phys. Chem. 100, 13293-13310 (1996).
22. Ishima, R. & Torchia, D.A. Protein dynamics from NMR. Nat. Struct. Biol. 7, 740-743 (2000).
23. Palmer, A.G., Grey, M.J. & Wang, C. Solution NMR spin relaxation methods for characterizing chemical exchange in high-molecular-weight systems. Methods Enzymol. 394, 430-465 (2005).
24. Henzler-Wildman, K. & Kern, D. Dynamic personalities of proteins. Nature 450, 964-972 (2007).
25. Mulder, F.A., Mittermaier, A., Hon, B., Dahlquist, F.W. & Kay, L.E. Studying excited states of proteins by NMR spectroscopy. Nat. Struct. Biol. 8, 932-935 (2001).
26. Mittag, T., Schaffhausen, B. & Gunther, U.L. Direct observation of protein-ligand interaction kinetics. Biochemistry 42, 11128-11136 (2003).
27. Tang, C., Iwahara, J. & Clore, G.M. Visualization of transient encounter complexes in protein-protein association. Nature 444, 383-386 (2006).
28. Iwahara, J. & Clore, G.M. Detecting transient intermediates in macromolecular binding by paramagnetic NMR. Nature 440, 1227-1230 (2006).
29. Sugase, K., Lansing, J.C., Dyson, H.J. & Wright, P.E. Tailoring relaxation dispersion experiments for fast-associating protein complexes. J. Am. Chem. Soc. 129, 13406-13407 (2007).
30. Sugase, K., Dyson, H.J. & Wright, P.E. Mechanism of coupled folding and binding of an intrinsically disordered protein. Nature 447, 1021-1025 (2007).
31. Tang, C., Schwieters, C.D. & Clore, G.M. Open-to-closed transition in apo maltosebinding protein observed by paramagnetic NMR. Nature 449, 1078-1082 (2007).
32. Korzhnev, D.M., Bezsonova, I., Lee, S., Chalikian, T.V. & Kay, L.E. Alternate binding modes for a ubiquitin-SH3 domain interaction studied by NMR spectroscopy. J. Mol. Biol. 386, 391-405 (2009).
33. Bruschweiler, S. et al. Direct observation of the dynamic process underlying allosteric signal transmission. J. Am. Chem. Soc. 131, 3063-3068 (2009)
34. Ishima, R., Freedberg, D.I., Wang, Y.-X., Louis, J.M. & Torchia, D.A. Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease, and their implications for function. Structure 7, 1047-1055 (1999).
35. Cole, R. & Loria, J.P. Evidence for flexibility in the function of ribonuclease A. Biochemistry 41, 6072-6081 (2002).
36. Eisenmesser, E.Z., Bosco, D.A., Akke, M. & Kern, D. Enzyme dynamics during catalysis. Science 295, 1520-1523 (2002).
37. Venkitakrishnan, R.P. et al. Conformational changes in the active site loops of dihydrofolate reductase during the catalytic cycle. Biochemistry 43, 16046-16055 (2004).
38. Wolf-Watz, M. et al. Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair. Nat. Struct. Mol. Biol. 11, 945-949 (2004).
39. Eisenmesser, E.Z. et al. Intrinsic dynamics of an enzyme underlies catalysis. Nature 438, 117-121 (2005).
40. Vallurupalli, P. & Kay, L.E. Complementarity of ensemble and single-molecule measures of protein motion: a relaxation dispersion NMR study of an enzyme complex. Proc. Natl. Acad. Sci. USA 103, 11910-11915 (2006).
41. Watt, E.D., Shimada, H., Kovrigin, E.L. & Loria, J.P. The mechanism of rate-limiting motions in enzyme function. Proc. Natl. Acad. Sci. USA 104, 11981-11986 (2007).
42. Kempf, J.G., Jung, J.Y., Ragain, C., Sampson, N.S. & Loria, J.P. Dynamic requirements for a functional protein hinge. J. Mol. Biol. 368, 131-149 (2007).
43. Tang, C., Louis, J.M., Aniana, A., Suh, J.Y. & Clore, G.M. Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease. Nature 455, 693-696 (2008).
44. Hill, R.B., Bracken, C., DeGrado, W.F. & Palmer, A.G. Molecular motions and protein folding: characterization of the backbone dynamics and folding equilibrium of α2D using 13C NMR spin relaxation. J. Am. Chem. Soc. 122, 11610-11619 (2000).
45. Korzhnev, D.M. et al. Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR. Nature 430, 586-590 (2004).
46. Choy, W.Y., Zhou, Z., Bai, Y. & Kay, L.E. An 15N NMR spin relaxation dispersion study of the folding of a pair of engineered mutants of apocy tochrome b562. J. Am. Chem. Soc. 127, 5066-5072 (2005).
47. Zeeb, M. & Balbach, J. Millisecond protein folding studied by NMR spectroscopy. Protein Pept. Lett. 12, 139-146 (2005).
48. Korzhnev, D.M., Neudecker, P., Zarrine-Afsar, A., Davidson, A.R. & Kay, L.E. Abp1p and Fyn SH3 domains fold through similar low-populated intermediate states. Biochemistry 45, 10175-10183 (2006).
49. Tang, Y., Grey, M.J., McKnight, J., Palmer, A.G. III & Raleigh, D.P. Multistate folding of the villin headpiece domain. J. Mol. Biol. 355, 1066-1077 (2006).
50. Neudecker, P. et al. Identification of a collapsed intermediate with non-native longrange interactions on the folding pathway of a pair of Fyn SH3 domain mutants by NMR relaxation dispersion spectroscopy. J. Mol. Biol. 363, 958-976 (2006).
51. Neudecker, P., Zarrine-Afsar, A., Davidson, A.R. & Kay, L.E. Phi-value analysis of a three-state protein folding pathway by NMR relaxation dispersion spectroscopy. Proc. Natl. Acad. Sci. USA 104, 15717-15722 (2007).
52. Korzhnev, D.M., Religa, T.L., Lundstrom, P., Fersht, A.R. & Kay, L.E. The folding pathway of an FF domain: characterization of an on-pathway intermediate state under folding conditions by (15)N, (13)C(alpha) and (13)C-methyl relaxation dispersion and (1)H/(2)H-exchange NMR spectroscopy. J. Mol. Biol. 372, 497-512 (2007).
53. Clore, G.M. Visualizing lowly-populated regions of the free energy landscape of macromolecular complexes by paramagnetic relaxation enhancement. Mol. Biosyst. 4, 1058-1069 (2008).
54. Carr, H.Y. & Purcell, E.M. Effects of diffusion on free precession in nuclear magnetic resonance experiments. Phys. Rev. 94, 630-638 (1954).
55. Meiboom, S. & Gill, D. Modified spin-echo method for measuring nuclear relaxation times. Rev. Sci. Instrum. 29, 688-691 (1958).
56. Solomon, I. Relaxation processes in a system of two spins. Phys. Rev. 99, 559-565 (1955).
57. Korzhnev, D.M. & Kay, L.E. Probing invisible, low-populated states of protein molecules by relaxation dispersion NMR spectroscopy: an application to protein folding. Acc. Chem. Res. 41, 442-451 (2008).
58. Lundstrom, P., Vallurupalli, P., Hansen, D.F. & Kay, L.E. Isotope labeling methods for studies of excited protein states by relaxation dispersion NMR spectroscopy. Nat. Protoc. (in the press).
59. Vallurupalli, P., Hansen, D.F. & Kay, L.E. Structures of invisible, excited protein states by relaxation dispersion NMR spectroscopy. Proc. Natl. Acad. Sci. USA 105, 11766-11771 (2008).
60. Clore, G.M. & Iwahara, J. Theory, practice, and applications of paramagnetic relaxation enhancement for the characterization of transient low-population states of biological macromolecules and their complexes. Chem. Rev. 109, 4108-4139 (2009).
61. Bai, Y., Sosnick, T., Mayne, L. & Englander, S. Protein folding intermediates: nativestate hydrogen exchange. Science 269, 192-197 (1995).
62. Englander, S.W., Mayne, L. & Krishna, M.M. Protein folding and misfolding: mechanism and principles. Q. Rev. Biophys. 40, 287-326 (2007).
63. Smock, R.G. & Gierasch, L.M. Sending signals dynamically. Science 324, 198-203 (2009).
64. Verkhivker, G.M. et al. Complexity and simplicity of ligand-macromolecule interactions: the energy landscape perspective. Curr. Opin. Struct. Biol. 12, 197-203 (2002).
65. Lange, O.F. et al. Recognition dynamics up to microseconds revealed from an RDCderived ubiquitin ensemble in solution. Science 320, 1471-1475 (2008).
66. Wolfenden, R. & Snider, M.J. The depth of chemical time and the power of enzymes as catalysts. Acc. Chem. Res. 34, 938-945 (2001).
67. Olsson, M.H., Parson, W.W. & Warshel, A. Dynamical contributions to enzyme catalysis: critical tests of a popular hypothesis. Chem. Rev. 106, 1737-1756 (2006).
68. Nagel, Z.D. & Klinman, J.P. A 21st century revisionist's view at a turning point in enzymology. Nat. Chem. Biol. 5, 543-550 (2009).
69. Pauling, L. Nature of forces between large molecules of biological interest. Nature 161, 707-709 (1948).
70. Hammes, G.G. Multiple conformational changes in enzyme catalysis. Biochemistry 41, 8221-8228 (2002).
71. Vamvaca, K., Vogeli, B., Kast, P., Pervushin, K. & Hilvert, D. An enzymatic molten globule: efficient coupling of folding and catalysis. Proc. Natl. Acad. Sci. USA 101, 12860-12864 (2004).
72. Roca, M., Messer, B., Hilvert, D. & Warshel, A. On the relationship between folding and chemical landscapes in enzyme catalysis. Proc. Natl. Acad. Sci. USA 105, 13877-13882 (2008).
73. Fierke, C.A., Johnson, K.A. & Benkovic, S.J. Construction and evaluation of the kinetic scheme associated with dihydrofolate reductase from Escherichia coli. Biochemistry 26, 4085-4092 (1987).
74. Boehr, D.D., McElheny, D., Dyson, H.J. & Wright, P.E. The dynamic energy landscape of dihydrofolate reductase catalysis. Science 313, 1638-1642 (2006).
75. Boehr, D.D., Dyson, H.J. & Wright, P.E. Conformational relaxation following hydride transfer plays a limiting role in dihydrofolate reductase catalysis. Biochemistry 47, 9227-9233 (2008).
76. Kubelka, J., Chiu, T.K., Davies, D.R., Eaton, W.A. & Hofrichter, J. Sub-microsecond protein folding. J. Mol. Biol. 359, 546-553 (2006).
77. Farrow, N.A., Zhang, O., Forman-Kay, J.D. & Kay, L.E. Comparison of the backbone dynamics of a folded and an unfolded SH3 domain existing in equilibrium in aqueous buffer. Biochemistry 34, 868-878 (1995).
78. Aronsson, G., Brorsson, A.-C., Sahlman, L. & Jonsson, B.-H. Remarkably slow folding of a small protein. FEBS Lett. 411, 359-364 (1997).
79. Zarrine-Afsar, A. et al. Theoretical and experimental demonstration of the importance of specific nonnative interactions in protein folding. Proc. Natl. Acad. Sci. USA 105, 9999-10004 (2008).
80. Plaxco, K.W. et al. The folding kinetics and thermodynamics of the Fyn-SH3 domain. Biochemistry 37, 2529-2537 (1998).
81. Di Nardo, A.A. et al. Dramatic acceleration of protein folding by stabilization of a nonnative backbone conformation. Proc. Natl. Acad. Sci. USA 101, 7954-7959 (2004).
82. Maity, H., Maity, M., Krishna, M.M., Mayne, L. & Englander, S.W. Protein folding: the stepwise assembly of foldon units. Proc. Natl. Acad. Sci. USA 102, 4741-4746 (2005).
83. Fersht, A.R. From the first protein structures to our current knowledge of protein folding: delights and scepticisms. Nat. Rev. Mol. Cell Biol. 9, 650-654 (2008).
84. Whittaker, S.B., Spence, G.R., Gunter Grossmann, J., Radford, S.E. & Moore, G.R. NMR analysis of the conformational properties of the trapped on-pathway folding intermediate of the bacterial immunity protein Im7. J. Mol. Biol. 366, 1001-1015 (2007).
85. Sprangers, R., Gribun, A., Hwang, P.M., Houry, W.A. & Kay, L.E. Quantitative NMR spectroscopy of supramolecular complexes: dynamic side pores in ClpP are important for product release. Proc. Natl. Acad. Sci. USA 102, 16678-16683 (2005).
86. Sprangers, R. & Kay, L.E. Quantitative dynamics and binding studies of the 20S proteasome by NMR. Nature 445, 618-622 (2007).
87. Loria, J.P., Rance, M. & Palmer, A.G.A. Relaxation-compensated (Carr Purcell Meiboom Gill) sequence for characterizing chemical exchange by NMR spectroscopy. J. Am. Chem. Soc. 121, 2331-2332 (1999).
88. Tollinger, M., Skrynnikov, N.R., Mulder, F.A., Forman-Kay, J.D. & Kay, L.E. Slow dynamics in folded and unfolded states of an SH3 domain. J. Am. Chem. Soc. 123, 11341-11352 (2001).
89. Ishima, R. & Torchia, D.A. Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach. J. Biomol. NMR 25, 243-248 (2003).
90. Lundstrom, P. et al. Fractional 13C enrichment of isolated carbons using [1-13C]- or [2- 13C]-glucose facilitates the accurate measurement of dynamics at backbone Calpha and side-chain methyl positions in proteins. J. Biomol. NMR 38, 199-212 (2007).
91. Hansen, D.F., Vallurupalli, P., Lundstrom, P., Neudecker, P. & Kay, L.E. Probing chemical shifts of invisible states of proteins with relaxation dispersion NMR spectroscopy: how well can we do? J. Am. Chem. Soc. 130, 2667-2675 (2008).
92. Ishima, R., Baber, J., Louis, J.M. & Torchia, D.A. Carbonyl carbon transverse relaxation dispersion measurements and ms-micros timescale motion in a protein hydrogen bond network. J. Biomol. NMR 29, 187-198 (2004).
93. Vallurupalli, P., Hansen, D.F., Stollar, E., Meirovitch, E. & Kay, L.E. Measurement of bond vector orientations in invisible excited states of proteins. Proc. Natl. Acad. Sci. USA 104, 18473-18477 (2007).
94. Hansen, D.F., Vallurupalli, P. & Kay, L.E. Quantifying two-bond 1HN-13CO and onebond 1H(alpha)-13C(alpha) dipolar couplings of invisible protein states by spin-state selective relaxation dispersion NMR spectroscopy. J. Am. Chem. Soc. 130, 8397-8405 (2008).
95. Baldwin, A., Hansen, D.F., Vallurupalli, P. & Kay, L.E. Measurement of methyl axis orientations in invisible, excited states of proteins by relaxation dispersion NMR spectroscopy. J. Am. Chem. Soc. 131, 11939-11948 (2009).
96. Vallurupalli, P., Hansen, D.F. & Kay, L.E. Probing structure in invisible protein states with anisotropic NMR chemical shifts. J. Am. Chem. Soc. 130, 2734-2735 (2008).
97. Hansen, D.F., Vallurupalli, P. & Kay, L.E. Using relaxation dispersion NMR spectroscopy to determine the structures of excited, invisible protein states. J. Biomol. NMR 41, 113-120 (2008).
98. Lippens, G., Caron, L. & Smet, C. A microscopic view of chemical exchange: Monte Carlo simulation of molecular association. Concepts Magn. Reson. A 21A, 1-9 (2004).
99. Skrynnikov, N.R., Dahlquist, F.W. & Kay, L.E. Reconstructing NMR spectra of "invisible" excited protein states using HSQC and HMQC experiments. J. Am. Chem. Soc. 124, 12352-12360 (2002).