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Mapping the Cytochrome c Folding Landscape

Lyubovitsky, Julia G. and Gray, Harry B. and Winkler, Jay R. (2002) Mapping the Cytochrome c Folding Landscape. Journal of the American Chemical Society, 124 (19). pp. 5481-5485. ISSN 0002-7863. doi:10.1021/ja017399r.

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The solution to the riddle of how a protein folds is encoded in the conformational energy landscape for the constituent polypeptide. Employing fluorescence energy transfer kinetics, we have mapped the S. cerevisiae iso-1 cytochrome c landscape by monitoring the distance between a C-terminal fluorophore and the heme during folding. Within 1 ms after denaturant dilution to native conditions, unfolded protein molecules have evolved into two distinct and rapidly equilibrating populations:  a collection of collapsed structures with an average fluorophore−heme distance (r̄) of 27 Å and a roughly equal population of extended polypeptides with r̄ > 50 Å. Molecules with the native fold appear on a time scale regulated by heme ligation events (∼300 ms, pH 7). The experimentally derived landscape for folding has a narrow central funnel with a flat upper rim on which collapsed and extended polypeptides interchange rapidly in a search for the native structure.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Gray, Harry B.0000-0002-7937-7876
Winkler, Jay R.0000-0002-4453-9716
Additional Information:© 2002 American Chemical Society. Received 26 October 2001. Published online 20 April 2002. Published in print 1 May 2002. We thank Jason Telford, Michael Machczynski, and I-Jy Chang for assistance during the initial stages of this project. This work was supported by the NSF (MCB-9974477, DBI-9876443), an NIH training grant and NSF graduate fellowship (J.G.L.), and the Arnold and Mabel Beckman Foundation.
Funding AgencyGrant Number
NIH Predoctoral FellowshipUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Issue or Number:19
Record Number:CaltechAUTHORS:20170411-132345490
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Official Citation:Mapping the Cytochrome c Folding Landscape Julia G. Lyubovitsky, Harry B. Gray, and Jay R. Winkler Journal of the American Chemical Society 2002 124 (19), 5481-5485 DOI: 10.1021/ja017399r
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76516
Deposited By: Ruth Sustaita
Deposited On:11 Apr 2017 21:03
Last Modified:15 Nov 2021 17:00

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