Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Dynamic personalities of proteins

Nature volume 450, pages 964–972 (2007)Cite this article

Abstract

Because proteins are central to cellular function, researchers have sought to uncover the secrets of how these complex macromolecules execute such a fascinating variety of functions. Although static structures are known for many proteins, the functions of proteins are governed ultimately by their dynamic character (or 'personality'). The dream is to 'watch' proteins in action in real time at atomic resolution. This requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The energy landscape defines the amplitude and timescale of protein motions.
Figure 2: Microsecond-to-millisecond protein dynamics are necessary for catalysis and are an intrinsic property of CYPA as shown by NMR relaxation dispersion experiments.
Figure 3: Single-molecule FRET reveals ordered, stepwise rotation of F0F1-ATP synthase on the millisecond timescale during ATP hydrolysis and synthesis.
Figure 4: Time dependence of carbon-monoxide migration and corresponding structural relaxation in myoglobin, using picosecond time-resolved X-ray crystallography.
Figure 5: The role of protein dynamics in molecular recognition by calmodulin on a range of timescales.
Figure 6: Ion-channel selectivity investigated by X-ray crystallography and molecular-dynamics simulations.
Figure 7: A hierarchy of protein dynamics in space and time underlies enzyme catalysis, using the enzyme adenylate kinase as an example.

Similar content being viewed by others

References

  1. Chandler, D. Roles of classical dynamics and quantum dynamics on activated processes occurring in liquids. J. Stat. Phys. 42, 49–67 (1986).

    Article  ADS  Google Scholar 

  2. Olsson, M. H. M., Parson, W. W. & Warshel, A. Dynamical contributions to enzyme catalysis: critical tests of a popular hypothesis. Chem. Rev. 106, 1737–1756 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Benkovic, S. J. & Hammes-Schiffer, S. A perspective on enzyme catalysis. Science 301, 1196–1202 (2003).

    Article  CAS  PubMed  ADS  Google Scholar 

  4. Gertner, B. J., Wilson, K. R. & Hynes, J. T. Nonequilibrium solvation effects on reaction-rates for model SN2 reactions in water. J. Chem. Phys. 90, 3537–3558 (1989).

    Article  CAS  ADS  Google Scholar 

  5. Schliwa, M. (ed.) Molecular Motors (Wiley, Weinheim, 2003).

    Google Scholar 

  6. Kolomeisky, A. B. & Fisher, M. E. Molecular motors: a theorist's perspective. Annu. Rev. Phys. Chem. 58, 675–695 (2007).

    Article  CAS  PubMed  ADS  Google Scholar 

  7. Lazaridis, T. & Karplus, M. 'New view' of protein folding reconciled with the old through multiple unfolding simulations. Science 278, 1928–1931 (1997).

    Article  CAS  PubMed  ADS  Google Scholar 

  8. Leopold, P. E., Montal, M. & Onuchic, J. N. Protein folding funnels — a kinetic approach to the sequence structure relationship. Proc. Natl Acad. Sci. USA 89, 8721–8725 (1992).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  9. Wolynes, P. G. Recent successes of the energy landscape theory of protein folding and function. Q. Rev. Biophys. 38, 405–410 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Austin, R. H., Beeson, K. W., Eisenstein, L., Frauenfelder, H. & Gunsalus, I. C. Dynamics of ligand binding to myoglobin. Biochemistry 14, 5355–5373 (1975).

    Article  CAS  PubMed  Google Scholar 

  11. Frauenfelder, H., Sligar, S. G. & Wolynes, P. G. The energy landscapes and motions of proteins. Science 254, 1598–1603 (1991).

    Article  CAS  PubMed  ADS  Google Scholar 

  12. Frauenfelder, H., Petsko, G. A. & Tsernoglou, D. Temperature-dependent X-ray diffraction as a probe of protein structural dynamics. Nature 280, 558–563 (1979).

    Article  CAS  PubMed  ADS  Google Scholar 

  13. Brooks, C. L. & Karplus, M. Solvent effects on protein motion and protein effects on solvent motion — dynamics of the active-site region of lysozyme. J. Mol. Biol. 208, 159–181 (1989).

    Article  CAS  PubMed  Google Scholar 

  14. Fenimore, P. W., Frauenfelder, H., McMahon, B. H. & Parak, F. G. Slaving: solvent fluctuations dominate protein dynamics and functions. Proc. Natl Acad. Sci. USA 99, 16047–16051 (2002).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  15. Beece, D. et al. Solvent viscosity and protein dynamics. Biochemistry 19, 5147–5157 (1980).

    Article  CAS  PubMed  Google Scholar 

  16. Fenimore, P. W., Frauenfelder, H., McMahon, B. H. & Young, R. D. Bulk-solvent and hydration-shell fluctuations, similar to α- and β-fluctuations in glasses, control protein motions and functions. Proc. Natl Acad. Sci. USA 101, 14408–14413 (2004).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  17. Shakhnovich, E. Protein folding thermodynamics and dynamics: where physics, chemistry, and biology meet. Chem. Rev. 106, 1559–1588 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lindorff-Larsen, K., Rogen, P., Paci, E., Vendruscolo, M. & Dobson, C. M. Protein folding and the organization of the protein topology universe. Trends Biochem. Sci. 30, 13–19 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Bourgeois, D. & Royant, A. Advances in kinetic protein crystallography. Curr. Opin. Struct. Biol. 15, 538–547 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Schlichting, I. et al. The catalytic pathway of cytochrome P450cam at atomic resolution. Science 287, 1615–1622 (2000).

    Article  CAS  PubMed  ADS  Google Scholar 

  21. Englander, S. W. Hydrogen exchange and mass spectrometry: a historical perspective. J. Am. Soc. Mass Spectrom. 17, 1481–1489 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bai, Y. W. Protein folding pathways studied by pulsed- and native-state hydrogen exchange. Chem. Rev. 106, 1757–1768 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Mittermaier, A. & Kay, L. E. New tools provide new insights in NMR studies of protein dynamics. Science 312, 224–228 (2006).

    Article  CAS  PubMed  ADS  Google Scholar 

  24. Kay, L. E. NMR studies of protein structure and dynamics. J. Magn. Reson. 173, 193–207 (2005).

    Article  CAS  PubMed  ADS  Google Scholar 

  25. Palmer, A. G. NMR characterization of the dynamics of biomacromolecules. Chem. Rev. 104, 3623–3640 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Kern, D., Eisenmesser, E. Z. & Wolf-Watz, M. Enzyme dynamics during catalysis measured by NMR spectroscopy. Methods Enzymol. 394, 507–524 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Pervushin, K., Riek, R., Wider, G. & Wuthrich, K. Attenuated T-2 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. Proc. Natl Acad. Sci. USA 94, 12366–12371 (1997).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  28. 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).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  29. Palmer, A. G., Grey, M. J. & Wang, C. Y. Solution NMR spin relaxation methods for characterizing chemical exchange in high-molecular-weight systems. Methods Enzymol. 394, 430–465 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Tugarinov, V. & Kay, L. E. Quantitative C-13 and H-2 NMR relaxation studies of the 723-residue enzyme malate synthase G reveal a dynamic binding interface. Biochemistry 44, 15970–15977 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Sprangers, R. & Kay, L. E. Quantitative dynamics and binding studies of the 20S proteasome by NMR. Nature 445, 618–622 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Horst, R. et al. Direct NMR observation of a substrate protein bound to the chaperonin GroEL. Proc. Natl Acad. Sci. USA 102, 12748–12753 (2005).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  33. Christodoulou, J. et al. Heteronuclear NMR investigations of dynamic regions of intact Escherichia coli ribosomes. Proc. Natl Acad. Sci. USA 101, 10949–10954 (2004).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  34. 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).

    Article  CAS  Google Scholar 

  35. Eisenmesser, E. Z., Bosco, D. A., Akke, M. & Kern, D. Enzyme dynamics during catalysis. Science 295, 1520–1523 (2002).

    Article  CAS  PubMed  ADS  Google Scholar 

  36. Eisenmesser, E. Z. et al. Intrinsic dynamics of an enzyme underlies catalysis. Nature 438, 117–121 (2005).

    Article  CAS  PubMed  ADS  Google Scholar 

  37. Fischer, G., Wittmannliebold, B., Lang, K., Kiefhaber, T. & Schmid, F. X. Cyclophilin and peptidyl-prolyl cis–trans isomerase are probably identical proteins. Nature 337, 476–478 (1989).

    Article  CAS  PubMed  ADS  Google Scholar 

  38. Takahashi, N., Hayano, T. & Suzuki, M. Peptidyl-prolyl cis–trans isomerase is the cyclosporin-A-binding protein cyclophilin. Nature 337, 473–475 (1989).

    Article  CAS  PubMed  ADS  Google Scholar 

  39. Loria, J. P., Rance, M. & Palmer, A. G. A TROSY CPMG sequence for characterizing chemical exchange in large proteins. J. Biomol. NMR 15, 151–155 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Tollinger, M., Skrynnikov, N. R., Mulder, F. A. 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).

    Article  CAS  PubMed  Google Scholar 

  41. Michalet, X., Weiss, S. & Jager, M. Single-molecule fluorescence studies of protein folding and conformational dynamics. Chem. Rev. 106, 1785–1813 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Myong, S., Stevens, B. C. & Ha, T. Bridging conformational dynamics and function using single-molecule spectroscopy. Structure 14, 633–643 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Yang, H. et al. Protein conformational dynamics probed by single-molecule electron transfer. Science 302, 262–266 (2003).

    Article  CAS  PubMed  ADS  Google Scholar 

  44. Deniz, A. A., Mukhopadhyay, S. & Lemke, E. A. Single-molecule biophysics: at the interface of biology, physics and chemistry. J. R. Soc. Interface advance online publication, doi:10.1098/rsif.2007.1021 (22 May 2007).

  45. Stryer, L. & Haugland, R. P. Energy transfer — a spectroscopic ruler. Proc. Natl Acad. Sci. USA 58, 719–726 (1967).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  46. Diez, M. et al. Proton-powered subunit rotation in single membrane-bound F0F1-ATP synthase. Nature Struct. Mol. Biol. 11, 135–141 (2004).

    Article  CAS  Google Scholar 

  47. Adcock, S. A. & McCammon, J. A. Molecular dynamics: survey of methods for simulating the activity of proteins. Chem. Rev. 106, 1589–1615 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. McCammon, J. A., Gelin, B. R. & Karplus, M. Dynamics of folded proteins. Nature 267, 585–590 (1977).

    Article  CAS  PubMed  ADS  Google Scholar 

  49. Scheraga, H. A., Khalili, M. & Liwo, A. Protein-folding dynamics: overview of molecular simulation techniques. Annu. Rev. Phys. Chem. 58, 57–83 (2007).

    Article  CAS  PubMed  ADS  Google Scholar 

  50. Karplus, M. & Kushick, J. N. Method for estimating the configurational entropy of macromolecules. Macromolecules 14, 325–332 (1981).

    Article  CAS  ADS  Google Scholar 

  51. Ma, J. P. & Karplus, M. Ligand-induced conformational changes in ras p21: a normal mode and energy minimization analysis. J. Mol. Biol. 274, 114–131 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Haliloglu, T., Bahar, I. & Erman, B. Gaussian dynamics of folded proteins. Phys. Rev. Lett. 79, 3090–3093 (1997).

    Article  CAS  ADS  Google Scholar 

  53. Jacobs, D. J., Rader, A. J., Kuhn, L. A. & Thorpe, M. F. Protein flexibility predictions using graph theory. Proteins 44, 150–165 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Wells, S., Menor, S., Hespenheide, B. & Thorpe, M. F. Constrained geometric simulation of diffusive motion in proteins. Phys. Biol. 2, S127–S136 (2005).

    Article  CAS  PubMed  ADS  Google Scholar 

  55. Hamelberg, D., Mongan, J. & McCammon, J. A. Accelerated molecular dynamics: a promising and efficient simulation method for biomolecules. J. Chem. Phys. 120, 11919–11929 (2004).

    Article  CAS  PubMed  ADS  Google Scholar 

  56. Paci, E. & Karplus, M. Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulations. J. Mol. Biol. 288, 441–459 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Schlitter, J., Engels, M., Kruger, P., Jacoby, E. & Wollmer, A. Targeted molecular-dynamics simulation of conformational change — application to the T–R transition in insulin. Mol. Simul. 10, 291–308 (1993).

    Article  CAS  Google Scholar 

  58. Roux, B. The calculation of the potential of mean force using computer simulations. Comput. Phys. Commun. 91, 275–282 (1995).

    Article  CAS  ADS  Google Scholar 

  59. Dellago, C. & Bolhuis, P. G. Transition path sampling simulations of biological systems. Top. Curr. Chem. 268, 291–317 (2007).

    Article  CAS  Google Scholar 

  60. Merritt, E. A. Expanding the model: anisotropic displacement parameters in protein structure refinement. Acta Crystallogr. D Biol. Crystallogr. 55, 1109–1117 (1999).

    Article  CAS  PubMed  Google Scholar 

  61. Schotte, F., Soman, J., Olson, J. S., Wulff, M. & Anfinrud, P. A. Picosecond time-resolved X-ray crystallography: probing protein function in real time. J. Struct. Biol. 147, 235–246 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Frauenfelder, H., McMahon, B. H. & Fenimore, P. W. Myoglobin: the hydrogen atom of biology and a paradigm of complexity. Proc. Natl Acad. Sci. USA 100, 8615–8617 (2003).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  63. Franks, W. T. et al. Magic-angle spinning solid-state NMR spectroscopy of the β1 immunoglobulin binding domain of protein G (GB1): N-15 and C-13 chemical shift assignments and conformational analysis. J. Am. Chem. Soc. 127, 12291–12305 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. Lorieau, J. L. & McDermott, A. E. Conformational flexibility of a microcrystalline globular protein: order parameters by solid-state NMR spectroscopy. J. Am. Chem. Soc. 128, 11505–11512 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Akke, M., Bruschweiler, R. & Palmer, A. G. NMR order parameters and free-energy — an analytical approach and its application to cooperative Ca2+ binding by calbindin-D9k . J. Am. Chem. Soc. 115, 9832–9833 (1993).

    Article  CAS  Google Scholar 

  66. Jarymowycz, V. A. & Stone, M. J. Fast time scale dynamics of protein backbones: NMR relaxation methods, applications, and functional consequences. Chem. Rev. 106, 1624–1671 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Lee, A. L., Sharp, K. A., Kranz, J. K., Song, X. J. & Wand, A. J. Temperature dependence of the internal dynamics of a calmodulin–peptide complex. Biochemistry 41, 13814–13825 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Li, Z. G., Raychaudhuri, S. & Wand, A. J. Insights into the local residual entropy of proteins provided by NMR relaxation. Protein Sci. 5, 2647–2650 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yang, D. W. & Kay, L. E. Contributions to conformational entropy arising from bond vector fluctuations measured from NMR-derived order parameters: application to protein folding. J. Mol. Biol. 263, 369–382 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Brokx, R. D., Lopez, M. M., Vogel, H. J. & Makhatadze, G. I. Energetics of target peptide binding by calmodulin reveals different modes of binding. J. Biol. Chem. 276, 14083–14091 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Wintrode, P. L. & Privalov, P. L. Energetics of target peptide recognition by calmodulin: a calorimetric study. J. Mol. Biol. 266, 1050–1062 (1997).

    Article  CAS  PubMed  Google Scholar 

  72. Frederick, K. K., Marlow, M. S., Valentine, K. G. & Wand, A. J. Conformational entropy in molecular recognition by proteins. Nature 448, 325–329 (2007).

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  73. Best, R. B., Clarke, J. & Karplus, M. What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation analysis. J. Mol. Biol. 349, 185–203 (2005).

    Article  CAS  PubMed  Google Scholar 

  74. Evenas, J., Forsen, S., Malmendal, A. & Akke, M. Backbone dynamics and energetics of a calmodulin domain mutant exchanging between closed and open conformations. J. Mol. Biol. 289, 603–617 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Barbato, G., Ikura, M., Kay, L. E., Pastor, R. W. & Bax, A. Backbone dynamics of calmodulin studied by N-15 relaxation using inverse detected 2-dimensional NMR-spectroscopy — the central helix is flexible. Biochemistry 31, 5269–5278 (1992).

    Article  CAS  PubMed  Google Scholar 

  76. Chattopadhyaya, R., Meador, W. E., Means, A. R. & Quiocho, F. A. Calmodulin structure refined at 1.7 angstrom resolution. J. Mol. Biol. 228, 1177–1192 (1992).

    Article  CAS  PubMed  Google Scholar 

  77. Fallon, J. L. & Quiocho, F. A. A closed compact structure of native Ca2+–calmodulin. Structure 11, 1303–1307 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Johnson, C. K. Calmodulin, conformational states, and calcium signaling. A single-molecule perspective. Biochemistry 45, 14233–14246 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Torok, K., Tzortzopoulos, A., Grabarek, Z., Best, S. L. & Thorogate, R. Dual effect of ATP in the activation mechanism of brain Ca2+/calmodulin-dependent protein kinase II by Ca2+/calmodulin. Biochemistry 40, 14878–14890 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Doster, W., Cusack, S. & Petry, W. Dynamical transition of myoglobin revealed by inelastic neutron scattering. Nature 337, 754–756 (1989).

    Article  CAS  PubMed  ADS  Google Scholar 

  81. Zhong, D. P. Ultrafast catalytic processes in enzymes. Curr. Opin. Chem. Biol. 11, 174–181 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Zewail, A. H. 4D ultrafast electron diffraction, crystallography, and microscopy. Annu. Rev. Phys. Chem. 57, 65–103 (2006).

    Article  CAS  PubMed  ADS  Google Scholar 

  83. Doyle, D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69–77 (1998).

    Article  CAS  PubMed  ADS  Google Scholar 

  84. Chill, J. H., Louis, J. M., Baber, J. L. & Bax, A. Measurement of 15N relaxation in the detergent-solubilized tetrameric KcsA potassium channel. J. Biomol. NMR 36, 123–136 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Noskov, S. Y., Berneche, S. & Roux, B. Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands. Nature 431, 830–834 (2004).

    Article  CAS  PubMed  ADS  Google Scholar 

  86. Vonrhein, C., Schlauderer, G. J. & Schulz, G. E. Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases. Structure 3, 483–490 (1995).

    Article  CAS  PubMed  Google Scholar 

  87. Wolf-Watz, M. et al. Linkage between dynamics and catalysis in a thermophilic–mesophilic enzyme pair. Nature Struct. Mol. Biol. 11, 945–949 (2004).

    Article  CAS  Google Scholar 

  88. Henzler-Wildman, K. A. et al. Intrinsic motions along an enzymatic reaction trajectory. Nature 450, 838–844 (2007).

    Article  CAS  PubMed  ADS  Google Scholar 

  89. Henzler-Wildman, K. A. et al. A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature 450, 913–916 (2007).

    Article  CAS  PubMed  ADS  Google Scholar 

  90. Volkman, B. F., Lipson, D., Wemmer, D. E. & Kern, D. Two-state allosteric behavior in a single-domain signaling protein. Science 291, 2429–2433 (2001).

    Article  CAS  PubMed  ADS  Google Scholar 

  91. Tsai, C. J., Kumar, S., Ma, B. & Nussinov, R. Folding funnels, binding funnels, and protein function. Protein Sci. 8, 1181–1190 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Boehr, D. D., Dyson, H. J. & Wright, P. E. An NMR perspective on enzyme dynamics. Chem. Rev. 106, 3055–3079 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Ansari, A. et al. Protein states and protein quakes. Proc. Natl Acad. Sci. USA 82, 5000–5004 (1985).

    Article  CAS  PubMed  ADS  PubMed Central  Google Scholar 

  94. Clapperton, J. A., Martin, S. R., Smerdon, S. J., Gamblin, S. J. & Bayley, P. M. Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism. Biochemistry 41, 14669–14679 (2002).

    Article  CAS  PubMed  Google Scholar 

  95. Meador, W. E., Means, A. R. & Quiocho, F. A. Target enzyme recognition by calmodulin — 2.4-angstrom structure of a calmodulin–peptide complex. Science 257, 1251–1255 (1992).

    Article  CAS  PubMed  ADS  Google Scholar 

  96. Aoyagi, M., Arvai, A. S., Tainer, J. A. & Getzoff, E. D. Structural basis for endothelial nitric oxide synthase binding to calmodulin. EMBO J. 22, 766–775 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kuboniwa, H. et al. Solution structure of calcium-free calmodulin. Nature Struct. Biol. 2, 768–776 (1995).

    Article  CAS  PubMed  Google Scholar 

  98. Noskov, S. Y. & Roux, B. Ion selectivity in potassium channels. Biophys. Chem. 124, 279–291 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M. Börsch, P. Anfinrud and B. Roux for providing the original images of Figs 3, 4 and 6b.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, 02454, Massachusetts, USA

    Katherine Henzler-Wildman & Dorothee Kern

Authors
  1. Katherine Henzler-Wildman
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Dorothee Kern
    View author publications

    You can also search for this author inPubMed Google Scholar

Additional information

Correspondence should be addressed to D.K. ([email protected]).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henzler-Wildman, K., Kern, D. Dynamic personalities of proteins. Nature 450, 964–972 (2007). https://doi.org/10.1038/nature06522

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature06522

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing