Structural characterization of intrinsically disordered proteins by the combined use of NMR and SAXS

Biochemical Society Transactions

Volumn 40, Issue 5, 2012, Pages 956-962

  Sibille, Nathalie ^a   Bernadó, Pau ^a  

^a CENTRE DE BIOCHIMIE STRUCTURALE   (France)

Author keywords

Integrative method; Intrinsically disordered protein; Nuclear magnetic resonance (NMR); Protein dynamics; Small angle x ray scattering (SAXS)

Indexed keywords

CALMODULIN; INTRINSICALLY DISORDERED PROTEIN; PROTEIN; PROTEIN X; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; CHEMICAL REACTION KINETICS; HETERONUCLEAR SINGLE QUANTUM COHERENCE; HUMAN; MAGNETISM; NITROGEN NUCLEAR MAGNETIC RESONANCE; NUCLEAR OVERHAUSER EFFECT; PARAMAGNETIC EFFECT; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN SECONDARY STRUCTURE; PROTEIN STRUCTURE; PROTEIN UNFOLDING; PROTON NUCLEAR MAGNETIC RESONANCE; RESIDUAL DIPOLAR COUPLING; REVIEW; X RAY CRYSTALLOGRAPHY; CHEMICAL STRUCTURE; CHEMISTRY; NUCLEAR MAGNETIC RESONANCE; SMALL ANGLE SCATTERING; X RAY DIFFRACTION;

EUKARYOTA;

HUMANS; MODELS, MOLECULAR; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PROTEIN CONFORMATION; PROTEINS; SCATTERING, SMALL ANGLE; X-RAY DIFFRACTION;

EID: 84866643147     PISSN: 03005127     EISSN: 14708752     Source Type: Journal    
DOI: 10.1042/BST20120149     Document Type: Review

References (84)

1. Dunker, A.K., Brown, C.J., Lawson, J.D., Iakoucheva, L.M. and Obradovic, Z. (2002) Intrinsic disorder and protein function. Biochemistry 41, 6573-6582
2. Dyson, H.J. and Wright, P.E. (2005) Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6, 197-208
3. Xie, H., Vucetic, S., Iakoucheva, L.M., Oldfield, C.J., Dunker, A.K., Uversky, V.N. and Obradovic, Z. (2007) Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 6, 1882-1898
4. Tompa, P. and Fuxreiter, M. (2008) Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem. Sci. 33, 2-8
5. Dosztanyi, Z., Chen, J., Dunker, A.K., Simon, I. and Tompa, P. (2006) Disorder and sequence repeats in hub proteins and their implications for network evolution. J. Proteome Res. 5, 2985-2995
6. Haynes, C., Oldfield, C.J., Ji, F., Klitgord, N., Cusick, M.E., Radivojac, P., Uversky, V.N., Vidal, M. and Iakoucheva, L.M. (2006) Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes. PLoS Comput. Biol. 2, e100
7. Uversky, V.N., Oldfield, C.J. and Dunker, A.K. (2008) Intrinsically disordered proteins in human diseases: introducing the D2 concept. Annu. Rev. Biophys. 37, 215-246
8. Dyson, H.J. and Wright, P.E. (2004) Unfolded proteins and protein folding studied by NMR. Chem. Rev. 104, 3607-3622
9. Bernadó, P. and Svergun, D.I. (2012) Structural analysis of intrinsically disordered proteins by small-angle X-ray scattering. Mol. BioSyst. 8, 151-167
10. Receveur-Brechot, V. and Durand, D. (2012) How random are intrinsically disordered proteins? A small angle scattering perspective. Curr. Protein Pept. Sci. 13, 55-75
11. Bernadó, P. and Blackledge, M. (2010) Structural biology: proteins in dynamic equilibrium. Nature 468, 1046-1048
12. Rezaei-Ghaleh, N., Blackledge, M. and Zweckstetter, M. (2012) Intrinsically disordered proteins: from sequence and conformational properties toward drug discovery. ChemBioChem 13, 930-950
13. Wishart, D.S. and Case, D.A. (2001) Use of chemical shifts in macromolecular structure determination. Methods Enzymol. 338, 3-34
14. Tamiola, K., Acar, B. and Mulder, F.A. (2010) Sequence-specific random coil chemical shifts of intrinsically disordered proteins. J. Am. Chem. Soc. 132, 18000-18003
15. Jensen, M.R., Salmon, L., Nodet, G. and Blackledge, M. (2010) Defining conformational ensembles of intrinsically disordered and partially folded proteins directly from chemical shifts. J. Am. Chem. Soc. 132, 1270-1272
16. Camilloni, C., De Simone, A., Vranken, W.F. and Vendruscolo, M. (2012) Determination of secondary structure populations in disordered states of proteins using nuclear magnetic resonance chemical shifts. Biochemistry 51, 2224-2231
17. Landrieu, I., Lacosse, L., Leroy, A., Wieruszeski, J.M., Trivelli, X., Sillen, A., Sibille, N., Schwalbe, H., Saxena, K., Langer, T. and Lippens, G. (2006) NMR analysis of a tau phosphorylation pattern. J. Am. Chem. Soc. 128, 3575-3583
18. Pérez, Y., Gairí, M., Pons, M. and Bernadó, P. (2009) Structural characterization of the natively unfolded N-terminal domain of human c-Src kinase: insights into the role of phosphorylation of the unique domain. J. Mol. Biol. 391, 136-148
19. Sibille, N., Huvent, I., Fauquant, C., Verdegem, D., Amniai, L., Leroy, A., Wieruszeski, J.M., Lippens, G. and Landrieu, I. (2012) Structural characterization by NMR of the impact of phosphorylation in the proline-rich region of the disordered tau protein. Proteins 80, 454-462
20. Tjandra, N. and Bax, A. (1997) Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium, Science 278, 1111-1114
21. Getz, M., Sun, X., Casiano-Negroni, A., Zhang, Q. and Al-Hashimi, H.M. (2004) NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings. Biopolymers 73, 380-403
22. Bax, A. (2003) Weak alignment offers new NMR opportunities to study protein structure and dynamics. Protein Sci. 12, 1-16
23. Louhivuori, M., Paakkonen, K., Fredriksson, K., Permi, P., Lounila, J. and Annila, A. (2003) On the origin of residual dipolar couplings from denatured proteins. J. Am. Chem. Soc. 125, 15647-15650
24. Mohana-Borges, R., Goto, N.K., Kroon, G.J., Dyson, H.J. and Wright, P.E. (2004) Structural characterization of unfolded states of apomyoglobin using residual dipolar couplings. J. Mol. Biol. 340, 1131-1142
25. Jensen, M.R., Houben, K., Lescop, E., Blanchard, L., Ruigrok, R.W.H. and Blackledge, M. (2008) Quantitative conformational analysis of partially folded proteins from residual dipolar couplings: application to the molecular recognition element of Sendai virus nucleoprotein. J. Am. Chem. Soc. 130, 8055-8061
26. Bernadó, P., Blanchard, L., Timmins, P., Marion, D., Ruigrok, R.W.H. and Blackledge, M. (2005) A structural model for unfolded proteins from residual dipolar couplings and small-angle X-ray scattering. Proc. Natl. Acad. Sci. U.S.A. 102, 17002-17007
27. Bernadó, P., Bertoncini, C.W., Griesinger, C., Zweckstetter, M. and Blackledge, M. (2005) Defining long-range order and local disorder in native α-synuclein using residual dipolar couplings. J. Am. Chem. Soc. 127, 17968-17969
28. Mukrasch, M.D., Markwick, P., Biernat, J., Bergen, M., Bernadó, P., Griesinger, C., Mandelkow, E., Zweckstetter, M. and Blackledge, M. (2007) Highly populated turn conformations in natively unfolded tau protein identified from residual dipolar couplings and molecular simulation. J. Am. Chem. Soc. 129, 5235-5243
29. Wells, M., Tidow, H., Rutherford, T.J., Markwick, P., Jensen, M.R., Mylonas, E., Svergun, D.I., Blackledge, M. and Fersht, A.R. (2008) Structure of tumor suppressor p53 and its intrinsically disordered N-terminal transactivation domain. Proc. Natl. Acad. Sci. U.S.A. 105, 5762-5767
30. Otting, G. (2010) Protein NMR using paramagnetic ions. Annu. Rev. Biophys. 39, 387-405
31. Clore, G.M. and Iwahara, J. (2009) 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
32. Lindorff-Larsen, K., Kristjansdottir, S., Teilum, K., Fieber, W., Dobson, C.M., Poulsen, F.M. and Vendruscolo, M. (2004) Determination of an ensemble of structures representing the denatured state of the bovine acyl-coenzyme A binding protein. J. Am. Chem. Soc. 126, 3291-3299
33. Salmon, L., Nodet, G., Ozenne, V., Yin, G., Jensen, M.R., Zweckstetter, M. and Blackledge, M. (2010) NMR characterization of long-range order in intrinsically disordered proteins. J. Am. Chem. Soc. 132, 8407-8418
34. Ganguly, D. and Chen, J. (2009) Structural interpretation of paramagnetic relaxation enhancement-derived distances for disordered protein states. J. Mol. Biol. 390, 467-477
35. Allison, J.R., Varnai, P., Dobson, C.M. and Vendruscolo, M. (2009) Determination of the free energy landscape of α-synuclein using spin label nuclear magnetic resonante measurements. J. Am. Chem. Soc. 131, 18314-18326
36. Fischer, M.W.F., Majumdar, A. and Zuiderweg, E.R.P. (1998) Protein NMR relaxation: theory, applications and outlook. Prog. Nucl. Magn. Reson. Spectrosc. 33, 207-272
37. Korzhnev, D.M., Billeter, M., Arseniev, A.S. and Orekhov, V.Y. (2001) NMR studies of brownian tumbling and internal motions in proteins. Prog. Nucl. Magn. Reson. Spectrosc. 38, 197-266
38. Lipari, G. and Szabo, A. (1982) Model-free approach to the interpretation of nuclear magnetic resonsnce relaxation in macromolecules. 1. Theory and range of validity. J. Am. Chem. Soc. 104, 4546-4558
39. Bracken, C. (2001) NMR spin relaxation methods for characterization of disorder and folding in proteins J. Mol. Graphics Modell. 19, 3-12
40. Peng, J.W. and Wagner, G. (1992) Mapping the spectral densities of N-H bond motions in eglin c using heteronuclear relaxation experiments. Biochemistry 31, 8571-8586
41. Klein-Seetharaman, J., Oikawa, M., Grimshaw, S.B., Wirmer, J., Duchardt, E., Ueda, T., Imoto, T., Smith, L.J., Dobson, C.M. and Schwalbe, H. (2002) Long-range interactions within a nonnative protein. Science 295, 1719-1722
42. Jensen, M.R., Communie, G., Ribeiro, Jr, E.A., Martinez, N., Desfosses, A., Salmon, L., Mollica, L., Gabel, F., Jamin, M., Longhi, S. et al. (2011) Intrinsic disorder in measles virus nucleocapsids. Proc. Natl. Acad. Sci. U.S.A. 108, 9839-9844
43. 0-P complex. PLoS Pathog. 7, e1002248
44. Stott, K., Watson, M., Howe, F.S., Grossman, J.G. and Thomas, J.O. (2010) Tail mediated collapse of HMGB1 is dynamic and occurs via differential binding of the acidic tail to the A and B domains. J. Mol. Biol. 403, 706-722
45. Jeffries, C.M., Lu, Y., Hynson, R.M., Taylor, J.E., Ballesteros, M., Kwan, A.H. and Trewhella, J. (2011) Human cardiac myosin binding protein C: structural flexibility within an extended modular architecture. J. Mol. Biol. 414, 735-748
46. Svergun, D.I. and Koch, M.H.J. (2003) Small-angle scattering studies of biological macromolecules in solution. Rep. Prog. Phys. 66, 1735-1782
47. Putnam, C.D., Hammel, M., Hura, G.L. and Tainer, J.A. (2007) X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution. Q. Rev. Biophys. 40, 191-285
48. Jacques, D.A. and Trewhella, J. (2010) Small-angle scattering for structural biology-expanding the frontier while avoiding the pitfalls. Protein Sci. 19, 642-567
49. Mertens, H.D. and Svergun, D.I. (2010) Structural characterization of proteins and complexes using small-angle X-ray solution scattering. J. Struct. Biol. 172, 128-141
50. Doniach, S. (2001) Changes in biomolecular conformation seen by small angle X-ray scattering. Chem. Rev. 101, 1763-1778
51. Pérez, J., Vachette, P., Russo, D., Desmandril, M. and Durand, D. (2001) Heat-induced unfolding of neocarzinostatin, a small all-β protein investigated by small-angle X-ray scattering. J. Mol. Biol. 308, 721-743
52. Bernadó, P. and Blackledge, M. (2009) A self-consistent description of the conformational behavior of chemically denatured proteins from NMR and small angle scattering. Biophys. J. 97, 2839-2845
53. Meier, S., Grzesiek, S. and Blackledge, M. (2007) Mapping the conformational landscape of urea-denatured ubiquitin using residual dipolar couplings. J. Am. Chem. Soc. 129, 9799-9807
54. Bernadó, P. (2010) Effect of interdomain dynamics on the structure determination of modular proteins by small-angle scattering. Eur. Biophys. J. 39, 769-780
55. Longhi, S., Receveur-Brechot, V., Karlin, D., Johansson, K., Darbon, H., Bhella, D., Yeo, R., Finet, S. and Canard, B. (2003) The C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein. J. Biol. Chem. 278, 18638-18648
56. + exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. Biochemistry 50, 3469-3480
57. Bernadó, P., Mylonas, E., Petoukhov, M.V., Blackledge, M. and Svergun, D.I. (2007) Structural characterization of flexible proteins using small-angle X-ray scattering. J. Am. Chem. Soc. 129, 5656-5664
58. Pelikan, M., Hura, G.L. and Hammel, M. (2009) Structure and flexibility within proteins as identified through small-angle X-ray scattering. Gen. Physiol. Biophys. 28, 174-189
59. Yang, S., Blachowicz, L., Makowski, L. and Roux, B. (2010) Multidomain assembled states of Hck tyrosine kinase in solution. Proc. Natl. Acad. Sci. U.S.A. 107, 15757-15762
60. Rozycki, B., Kim, Y.C. and Hummer, G. (2011) SAXS ensemble refinement of ESCRT-III CHMP3 conformational transitions. Structure 19, 109-116
61. Robinson, C.V., Sali, A. and Baumeister, W. (2007) The molecular sociology of the cell. Nature 450, 973-982
62. Bernadó, P. (2011) Low-resolution structural approaches to study biomolecular assemblies. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 1, 283-297
63. Grishaev, A., Wu, J., Trewhella, J. and Bax, J. (2005) Refinement of multidomain protein structures by combination of solution small-angle X-ray scattering and NMR data. J. Am. Chem. Soc. 127, 16621-16628
64. Wang, J., Zuo, X., Byeon, I.J., Jung, J., Wang, X., Dyba, M., Seifert, S., Schwieters, C.D., Quin, J., Gronenborn, A.M. and Wang, Y.X. (2009) Determination of multicomponent protein structures in solution using global orientation and shape restraints. J. Am. Chem. Soc. 131, 10507-10515
65. Schwieters, C.D., Suh, J.Y., Grishaev, A., Ghirlando, R., Takayama, Y. and Clore, G.M. (2010) Solution structure of the 128 kDa enzyme I dimer from Escherichia coli and its 146 kDa complex with HPr using residual dipolar couplings and small- and wide-angle X-ray scattering. J. Am. Chem. Soc. 132, 13026-13045
66. Zhou, H.X. (2004) Polymer models of protein stability, folding, and interactions. Biochemistry 43, 2141-2154
67. Fischer, C.K. and Stultz, C.M. (2011) Constructing ensembles for intrinsically disordered proteins. Curr. Opin. Struct. Biol. 21, 426-431
68. Ozenne, V., Bauer, F., Salmon, L., Huang, J.R., Jensen, M.R., Segard, S., Bernadó, P., Charavay, C. and Blackledge, M. (2012) Flexible-meccano: a tool for the generation of explicit ensemble descriptions of intrinsically disordered proteins and their associated experimental observables. Bioinformatics 28, 1463-1470
69. Jensen, M.R., Markwick, P.R., Meier, S., Griesinger, C., Zweckstetter, M., Grzesiek, S., Bernadó, P. and Blackledge, M. (2009) Quantitative determination of the conformational properties of partially folded and intrinsically disordered proteins using NMR dipolar couplings. Structure 17, 1169-1185
70. Vendruscolo, M. (2007) Determination of conformationally heterogeneous states of proteins. Curr. Opin. Struct. Biol. 17, 15-20
71. Jensen, M.R., Markwick, P.R., Meier, S., Griesinger, C., Zweckstetter, M., Grzesiek, S., Bernadó, P. and Blackledge, M. (2009) Quantitative determination of the conformational properties of partially folded and intrinsically disordered proteins using NMR dipolar couplings. Structure 17, 1169-1185
72. Schneider, R., Huang, J.R., Yao, M., Communie, G., Ozenne, V., Mollica, L., Salmon, L., Jensen, M.R. and Blackledge, M. (2012) Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy. Mol. BioSyst. 8, 58-68
73. Marsh, J.A., Neale, C., Jack, F.E., Choy, W.Y., Lee, A.Y., Crowhurst, K.A. and Forman-Kay, J.D. (2007) Improved structural characterizations of the drkN SH3 domain unfolded state suggest a compact ensemble with native-like and non-native structure. J. Mol. Biol. 367, 1494-1510
74. Marsh, J.A. and Forman-Kay, J.D. (2009) Structure and disorder in an unfolded state under nondenaturing conditions from ensemble models consistent with a large number of experimental restraints. J. Mol. Biol. 391, 359-374
75. Marsh, J.A. and Forman-Kay, J.D. (2011) Ensemble modeling of protein disordered states: experimental restraint contributions and validation. Proteins 80, 556-572
76. Mittag, T., Marsh, J., Grishaev, A., Orlicky, S., Sicheri, F., Tyers, M. and Forman-Kay, J.D. (2010) Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase. Structure 18, 494-506
77. Fisher, C.K., Huang, A. and Stultz, C.M. (2010) Modeling intrinsically disordered proteins with Bayesian statistics. J. Am. Chem. Soc. 132, 14919-14927
78. Ullman, O., Fisher, C.K. and Stultz, C.M. (2011) Explaining the structural plasticity of α-synuclein. J. Am. Chem. Soc. 133, 19536-19546
79. Bertini, I., Gianchetti, A., Luchinat, C., Parigi, G., Petoukhov, M.V., Pieratelli, R., Ravera, E. and Svergun, D.I. (2010) Conformational space of flexible biological macromolecules from average data. J. Am. Chem. Soc. 132, 13553-13558
80. Nagulapalli, M., Parigi, G., Yuan, J., Gsponer, J., Deraos, G., Bamm, V.V., Harauz, G., Matsoukas, J., de Planque, M.R., Gerothanassis, I.P. et al. (2012) Recognition pliability is coupled to structural heterogeneity: a calmodulin intrinsically disordered binding region complex. Structure 20, 522-533
81. Dasgupta, S., Hu, X., Keizers, P.H., Liu, W.M., Luchinat, C., Nagulapalli, M., Overhand, M., Parigi, G., Sgheri, L. and Ubbink, M. (2011) Narrowing the conformational space sampled by two-domain proteins with paramagnetic probes in both domains. J. Biomol. NMR 51, 253-263
82. Luchinat, C., Nagulapalli, M., Parigi, G. and Sgheri, L. (2012) Maximum occurrence analysis of protein conformations for different distributions of paramagnetic metal ions within flexible two-domain proteins. J. Magn. Reson. 215, 85-93
83. Bernadó, P., Modig, K., Grela, P., Svergun, D.I., Tchorzewski, M., Pons, M. and Akke, M. (2010) Structure and dynamics of ribosomal protein L12: an ensemble model based on SAXS and NMR relaxation. Biophys. J. 98, 2374-2382
84. Prompers, J.J. and Brüschweiler, R. (2002) General framework for studying the dynamics of folded and nonfolded proteins by NMR relaxation spectroscopy and MD simulation. J. Am. Chem. Soc. 124, 4522-4534