Structural characterization of a misfolded intermediate populated during the folding process of a PDZ domain

Nature Structural and Molecular Biology

Volumn 17, Issue 12, 2010, Pages 1431-1437

  Gianni, Stefano ^a   Ivarsson, Ylva ^a,c   De Simone, Alfonso ^b   Travaglini Allocatelli, Carlo ^a   Brunori, Maurizio ^a   Vendruscolo, Michele ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

SCAFFOLD PROTEIN;

AMINO TERMINAL SEQUENCE; ARTICLE; BETA SHEET; MOLECULAR MECHANICS; PDZ DOMAIN; PRIORITY JOURNAL; PROTEIN ENGINEERING; PROTEIN FOLDING; PROTEIN STRUCTURE; STRUCTURE ANALYSIS;

MODELS, MOLECULAR; MUTATION; PDZ DOMAINS; PROTEIN FOLDING; PROTEIN STRUCTURE, TERTIARY;

EID: 78649885501     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.1956     Document Type: Article

References (52)

1. Fersht, A.R. Structure and Mechanism in Protein Science (Freeman, New York, 1999).
2. Selkoe, D.J. Folding proteins in fatal ways. Nature 426, 900-904 (2003).
3. Chiti, F. & Dobson, C.M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333-366 (2006).
4. Frydman, J. Folding of newly translated proteins in vivo: the role of molecular chaperones. Annu. Rev. Biochem. 70, 603-647 (2001).
5. Hartl, F.U. & Hayer-Hartl, M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295, 1852-1858 (2002).
6. Bukau, B., Weissman, J. & Horwich, A. Molecular chaperones and protein quality control. Cell 125, 443-451 (2006).
7. Ellgaard, L. & Helenius, A. Quality control in the endoplasmic reticulum. Nat. Rev. Mol. Cell Biol. 4, 181-191 (2003).
8. Goldberg, A.L. Protein degradation and protection against misfolded or damaged proteins. Nature 426, 895-899 (2003).
9. Chiti, F. & Dobson, C.M. Amyloid formation by globular proteins under native conditions. Nat. Chem. Biol. 5, 15-22 (2009).
10. Elad, N. et al. Topologies of a substrate protein bound to the chaperonin GroEL. Mol. Cell 26, 415-426 (2007).
11. Hartl, F.U. & Hayer-Hartl, M. Converging concepts of protein folding in vitro and in vivo. Nat. Struct. Mol. Biol. 16, 574-581 (2009).
12. Horwich, A.L. & Fenton, W.A. Chaperonin-mediated protein folding: using a central cavity to kinetically assist polypeptide chain folding. Q. Rev. Biophys. 42, 83-116 (2009).
13. Matouschek, A., Kellis, J.T. Jr., Serrano, L., Bycroft, M. & Fersht, A.R. Transient folding intermediates characterized by protein engineering. Nature 346, 440-445 (1990).
14. Capaldi, A.P., Kleanthous, C. & Radford, S.E. Im7 folding mechanism: misfolding on a path to the native state. Nat. Struct. Biol. 9, 209-216 (2002).
15. Friel, C.T., Smith, D.A., Vendruscolo, M., Gsponer, J. & Radford, S.E. The mechanism of folding of Im7 reveals competition between functional and kinetic evolutionary constraints. Nat. Struct. Mol. Biol. 16, 318-324 (2009).
16. Ivarsson, Y., Travaglini-Allocatelli, C., Brunori, M. & Gianni, S. Engineered symmetric connectivity of secondary structure elements highlights malleability of protein folding pathways. J. Am. Chem. Soc. 131, 11727-11733 (2009).
17. Korzhnev, D.M., Religa, T.L., Banachewicz, W., Fersht, A.R. & Kay, L.E. A transient and low-populated protein-folding intermediate at atomic resolution. Science 329, 1312-1316 (2010).
18. Religa, T.L., Markson, J.S., Mayor, U., Freund, S.M. & Fersht, A.R. Solution structure of a protein denatured state and folding intermediate. Nature 437, 1053-1056 (2005).
19. Wu, Y., Vadrevu, R., Kathuria, S., Yang, X.Y. & Matthews, C.R. A tightly packed hydrophobic cluster directs the formation of an off-pathway sub-millisecond folding intermediate in the alpha subunit of tryptophan synthase, a TIM barrel protein. J. Mol. Biol. 366, 1624-1638 (2007).
20. Nabuurs, S.M., Westphal, A.H. & van Mierlo, C.P.M. Noncooperative formation of the off-pathway molten globule during folding of the alpha-beta parallel protein apofavodoxin. J. Am. Chem. Soc. 131, 2739-2746 (2009).
21. Ivarsson, Y., Travaglini-Allocatelli, C., Morea, V., Brunori, M. & Gianni, S. The folding pathway of an engineered circularly permuted PDZ domain. Protein Eng. Des. Sel. 21, 155-160 (2008).
22. Morais Cabral, J.H. et al. Crystal structure of a PDZ domain. Nature 382, 649-652 (1996).
23. Krojer, T., Garrido-Franco, M., Huber, R., Ehrmann, M. & Clausen, T. Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine. Nature 416, 455-459 (2002).
24. Liao, D.I., Qian, J., Chisholm, D.A., Jordan, D.B. & Diner, B.A. Crystal structures of the photosystem II D1 C-terminal processing protease. Nat. Struct. Biol. 7, 749-753 (2000).
25. Calosci, N. et al. Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins. Proc. Natl. Acad. Sci. USA 105, 19241-19246 (2008).
26. Chi, C.N. et al. A conserved folding mechanism for PDZ domains. FEBS Lett. 581, 1109-1113 (2007).
27. Gianni, S. et al. Kinetic folding mechanism of PDZ2 from PTP-BL. Protein Eng. Des. Sel. 18, 389-395 (2005).
28. Gianni, S. et al. A PDZ domain recapitulates a unifying mechanism for protein folding. Proc. Natl. Acad. Sci. USA 104, 128-133 (2007).
29. Ivarsson, Y. et al. An on-pathway intermediate in the folding of a PDZ domain. J. Biol. Chem. 282, 8568-8572 (2007).
30. Jemth, P. & Gianni, S. PDZ domains: folding and binding. Biochemistry 46, 8701-8708 (2007).
31. Ivarsson, Y., Travaglini-Allocatelli, C., Brunori, M. & Gianni, S. Folding and misfolding in a naturally occurring circularly permuted PDZ domain. J. Biol. Chem. 283, 8954-8960 (2008).
32. Fersht, A.R., Matouschek, A. & Serrano, L. The folding of an enzyme. I. Theory of protein engineering analysis of stability and pathway of protein folding. J. Mol. Biol. 224, 771-782 (1992).
33. Fersht, A.R. & Sato, S. Phi-value analysis and the nature of protein-folding transition states. Proc. Natl. Acad. Sci. USA 101, 7976-7981 (2004).
34. Mayor, U. et al. The complete folding pathway of a protein from nanoseconds to microseconds. Nature 421, 863-867 (2003).
35. Li, L., Mirny, L.A. & Shakhnovich, E.I. Kinetics, thermodynamics and evolution of non-native interactions in a protein folding nucleus. Nat. Struct. Biol. 7, 336-342 (2000).
36. Ozkan, S.B., Bahar, I. & Dill, K.A. Transition states and the meaning of Phi-values in protein folding kinetics. Nat. Struct. Biol. 8, 765-769 (2001).
37. Ventura, S. et al. Conformational strain in the hydrophobic core and its implications for protein folding and design. Nat. Struct. Biol. 9, 485-493 (2002).
38. Paci, E., Vendruscolo, M., Dobson, C.M. & Karplus, M. Determination of a transition state at atomic resolution from protein engineering data. J. Mol. Biol. 324, 151-163 (2002).
39. Vendruscolo, M., Paci, E., Dobson, C.M. & Karplus, M. Three key residues form a critical contact network in a protein folding transition state. Nature 409, 641-645 (2001).
40. Gsponer, J. et al. Determination of an ensemble of structures representing the intermediate state of the bacterial immunity protein Im7. Proc. Natl. Acad. Sci. USA 103, 99-104 (2006).
41. Salvatella, X., Dobson, C.M., Fersht, A.R. & Vendruscolo, M. Determination of the folding transition states of barnase by using PhiI-value-restrained simulations validated by double mutant PhiIJ-values. Proc. Natl. Acad. Sci. USA 102, 12389-12394 (2005).
42. Bryngelson, J.D., Onuchic, J.N., Socci, N.D. & Wolynes, P.G. Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins 21, 167-195 (1995).
43. Ferreiro, D.U., Hegler, J.A., Komives, E.A. & Wolynes, P.G. Localizing frustration in native proteins and protein assemblies. Proc. Natl. Acad. Sci. USA 104, 19819-19824 (2007).
44. Sutto, L., Lätzer, J., Hegler, J.A., Ferreiro, D.U. & Wolynes, P.G. Consequences of localized frustration for the folding mechanism of the IM7 protein. Proc. Natl. Acad. Sci. USA 104, 19825-19830 (2007).
45. Tartaglia, G.G. et al. Prediction of aggregation-prone regions in structured proteins. J. Mol. Biol. 380, 425-436 (2008).
46. Hubner, I.A., Lindberg, M., Haglund, E., Oliveberg, M. & Shakhnovich, E.I. Common motifs and topological effects in the protein folding transition state. J. Mol. Biol. 359, 1075-1085 (2006).
47. Lindberg, M., Tangrot, J. & Oliveberg, M. Complete change of the protein folding transition state upon circular permutation. Nat. Struct. Biol. 9, 818-822 (2002).
48. Lindberg, M.O. & Oliveberg, M. Malleability of protein folding pathways: a simple reason for complex behaviour. Curr. Opin. Struct. Biol. 17, 21-29 (2007).
49. Lindberg, M.O. et al. Folding of circular permutants with decreased contact order: general trend balanced by protein stability. J. Mol. Biol. 314, 891-900 (2001).
50. Klimov, D.K. & Thirumalai, D. Symmetric connectivity of secondary structure elements enhances the diversity of folding pathways. J. Mol. Biol. 353, 1171-1186 (2005).
51. Jemth, P. et al. Demonstration of a low-energy on-pathway intermediate in a fast-folding protein by kinetics, protein engineering, and simulation. Proc. Natl. Acad. Sci. USA 101, 6450-6455 (2004).
52. Jackson, S.E. & Fersht, A.R. Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition. Biochemistry 30, 10428-10435 (1991).