Diffusion-limited contact formation in unfolded cytochrome c: estimating the maximum rate of protein folding (original) (raw)

Abstract

How fast can a protein fold? The rate of polypeptide collapse to a compact state sets an upper limit to the rate of folding. Collapse may in turn be limited by the rate of intrachain diffusion. To address this question, we have determined the rate at which two regions of an unfolded protein are brought into contact by diffusion. Our nanosecond-resolved spectroscopy shows that under strongly denaturing conditions, regions of unfolded cytochrome separated by approximately 50 residues diffuse together in 35-40 microseconds. This result leads to an estimate of approximately (1 microsecond)-1 as the upper limit for the rate of protein folding.

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  1. Alexander P., Orban J., Bryan P. Kinetic analysis of folding and unfolding the 56 amino acid IgG-binding domain of streptococcal protein G. Biochemistry. 1992 Aug 18;31(32):7243–7248. doi: 10.1021/bi00147a006. [DOI] [PubMed] [Google Scholar]
  2. Baldwin R. L. Why is protein folding so fast? Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2627–2628. doi: 10.1073/pnas.93.7.2627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ballew R. M., Sabelko J., Gruebele M. Direct observation of fast protein folding: the initial collapse of apomyoglobin. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5759–5764. doi: 10.1073/pnas.93.12.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bryngelson J. D., Onuchic J. N., Socci N. D., Wolynes P. G. Funnels, pathways, and the energy landscape of protein folding: a synthesis. Proteins. 1995 Mar;21(3):167–195. doi: 10.1002/prot.340210302. [DOI] [PubMed] [Google Scholar]
  5. Bryngelson J. D., Wolynes P. G. Spin glasses and the statistical mechanics of protein folding. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7524–7528. doi: 10.1073/pnas.84.21.7524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Buckler D. R., Haas E., Scheraga H. A. Analysis of the structure of ribonuclease A in native and partially denatured states by time-resolved noradiative dynamic excitation energy transfer between site-specific extrinsic probes. Biochemistry. 1995 Dec 12;34(49):15965–15978. doi: 10.1021/bi00049a011. [DOI] [PubMed] [Google Scholar]
  7. Camacho C. J., Thirumalai D. Theoretical predictions of folding pathways by using the proximity rule, with applications to bovine pancreatic trypsin inhibitor. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1277–1281. doi: 10.1073/pnas.92.5.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dill K. A., Fiebig K. M., Chan H. S. Cooperativity in protein-folding kinetics. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1942–1946. doi: 10.1073/pnas.90.5.1942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elöve G. A., Bhuyan A. K., Roder H. Kinetic mechanism of cytochrome c folding: involvement of the heme and its ligands. Biochemistry. 1994 Jun 7;33(22):6925–6935. doi: 10.1021/bi00188a023. [DOI] [PubMed] [Google Scholar]
  10. Frenkel B., Bishara-Shieban J., Bar-Tana J. The effect of beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16) on plasma very-low-density lipoprotein metabolism in rats: role of apolipoprotein C-III. Biochem J. 1994 Mar 1;298(Pt 2):409–414. doi: 10.1042/bj2980409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gottfried D. S., Haas E. Nonlocal interactions stabilize compact folding intermediates in reduced unfolded bovine pancreatic trypsin inhibitor. Biochemistry. 1992 Dec 15;31(49):12353–12362. doi: 10.1021/bi00164a009. [DOI] [PubMed] [Google Scholar]
  12. Hofrichter J., Ansari A., Jones C. M., Deutsch R. M., Sommer J. H., Henry E. R. Ligand binding and conformational changes measured by time-resolved absorption spectroscopy. Methods Enzymol. 1994;232:387–415. doi: 10.1016/0076-6879(94)32056-x. [DOI] [PubMed] [Google Scholar]
  13. Huang G. S., Oas T. G. Submillisecond folding of monomeric lambda repressor. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6878–6882. doi: 10.1073/pnas.92.15.6878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones C. M., Henry E. R., Hu Y., Chan C. K., Luck S. D., Bhuyan A., Roder H., Hofrichter J., Eaton W. A. Fast events in protein folding initiated by nanosecond laser photolysis. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11860–11864. doi: 10.1073/pnas.90.24.11860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karplus M., Weaver D. L. Protein folding dynamics: the diffusion-collision model and experimental data. Protein Sci. 1994 Apr;3(4):650–668. doi: 10.1002/pro.5560030413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Karplus M., Weaver D. L. Protein-folding dynamics. Nature. 1976 Apr 1;260(5550):404–406. doi: 10.1038/260404a0. [DOI] [PubMed] [Google Scholar]
  17. Khorasanizadeh S., Peters I. D., Roder H. Evidence for a three-state model of protein folding from kinetic analysis of ubiquitin variants with altered core residues. Nat Struct Biol. 1996 Feb;3(2):193–205. doi: 10.1038/nsb0296-193. [DOI] [PubMed] [Google Scholar]
  18. Kragelund B. B., Robinson C. V., Knudsen J., Dobson C. M., Poulsen F. M. Folding of a four-helix bundle: studies of acyl-coenzyme A binding protein. Biochemistry. 1995 May 30;34(21):7217–7224. doi: 10.1021/bi00021a037. [DOI] [PubMed] [Google Scholar]
  19. Kuszewski J., Clore G. M., Gronenborn A. M. Fast folding of a prototypic polypeptide: the immunoglobulin binding domain of streptococcal protein G. Protein Sci. 1994 Nov;3(11):1945–1952. doi: 10.1002/pro.5560031106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leszczynski J. F., Rose G. D. Loops in globular proteins: a novel category of secondary structure. Science. 1986 Nov 14;234(4778):849–855. doi: 10.1126/science.3775366. [DOI] [PubMed] [Google Scholar]
  21. Nölting B., Golbik R., Fersht A. R. Submillisecond events in protein folding. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10668–10672. doi: 10.1073/pnas.92.23.10668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pascher T., Chesick J. P., Winkler J. R., Gray H. B. Protein folding triggered by electron transfer. Science. 1996 Mar 15;271(5255):1558–1560. doi: 10.1126/science.271.5255.1558. [DOI] [PubMed] [Google Scholar]
  23. Phillips C. M., Mizutani Y., Hochstrasser R. M. Ultrafast thermally induced unfolding of RNase A. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7292–7296. doi: 10.1073/pnas.92.16.7292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ptitsyn O. B. Molten globule and protein folding. Adv Protein Chem. 1995;47:83–229. doi: 10.1016/s0065-3233(08)60546-x. [DOI] [PubMed] [Google Scholar]
  25. Schindler T., Herrler M., Marahiel M. A., Schmid F. X. Extremely rapid protein folding in the absence of intermediates. Nat Struct Biol. 1995 Aug;2(8):663–673. doi: 10.1038/nsb0895-663. [DOI] [PubMed] [Google Scholar]
  26. Shoup D., Szabo A. Role of diffusion in ligand binding to macromolecules and cell-bound receptors. Biophys J. 1982 Oct;40(1):33–39. doi: 10.1016/S0006-3495(82)84455-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sosnick T. R., Mayne L., Hiller R., Englander S. W. The barriers in protein folding. Nat Struct Biol. 1994 Mar;1(3):149–156. doi: 10.1038/nsb0394-149. [DOI] [PubMed] [Google Scholar]
  28. Waldburger C. D., Jonsson T., Sauer R. T. Barriers to protein folding: formation of buried polar interactions is a slow step in acquisition of structure. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2629–2634. doi: 10.1073/pnas.93.7.2629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang J. C., Davidson N. On the probability of ring closure of lambda DNA. J Mol Biol. 1966 Aug;19(2):469–482. doi: 10.1016/s0022-2836(66)80017-7. [DOI] [PubMed] [Google Scholar]
  30. Wang J. C., Davidson N. Thermodynamic and kinetic studies on the interconversion between the linear and circular forms of phage lambda DNA. J Mol Biol. 1966 Jan;15(1):111–123. doi: 10.1016/s0022-2836(66)80213-9. [DOI] [PubMed] [Google Scholar]
  31. Williams S., Causgrove T. P., Gilmanshin R., Fang K. S., Callender R. H., Woodruff W. H., Dyer R. B. Fast events in protein folding: helix melting and formation in a small peptide. Biochemistry. 1996 Jan 23;35(3):691–697. doi: 10.1021/bi952217p. [DOI] [PubMed] [Google Scholar]