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Using deeply trapped intermediates to map the cytochrome c folding landscape

Tezcan, F. Akif and Findley, William M. and Crane, Brian R. and Ross, Scott A. and Lyubovitsky, Julia G. and Gray, Harry B. and Winkler, Jay R. (2002) Using deeply trapped intermediates to map the cytochrome c folding landscape. Proceedings of the National Academy of Sciences of the United States of America, 99 (13). pp. 8626-8630. ISSN 0027-8424. PMCID PMC124336. doi:10.1073/pnas.132254499.

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Replacement of iron with cobalt(III) selectively introduces a deep trap in the folding-energy landscape of the heme protein cytochrome c. Remarkably, neither the protein structure nor the folding thermodynamics is perturbed by this metal-ion substitution, as shown by data from spectroscopic and x-ray diffraction experiments. Through kinetics measurements, we have found parallel folding pathways involving several different misligated Co(III) species, and, as these folding intermediates persist for several hours under certain conditions, we have been able to elucidate fully their spectroscopic properties. The results, along with an analysis of the fluorescence energy-transfer kinetics during refolding, show that rapidly equilibrating populations of compact and extended polypeptide conformations are present until all molecules have reached the native structure. These measurements provide direct evidence that collapsed denatured structures are not substantially more stable than extended conformations of cytochrome c.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Tezcan, F. Akif0000-0002-4733-6500
Gray, Harry B.0000-0002-7937-7876
Winkler, Jay R.0000-0002-4453-9716
Additional Information:© 2002 by the National Academy of Sciences. Contributed by Harry B. Gray, April 30, 2002. This research was supported by the National Science Foundation (MCB 9974477; DBI 9876443) and the Arnold and Mabel Beckman Foundation. Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, (access code 015902) (PDB ID code 1LFM).
Funding AgencyGrant Number
Arnold and Mabel Beckman FoundationUNSPECIFIED
Subject Keywords:denatured state, energy landscape, microscopic theory, residual structure, electron-transfer, optical triggers, ribonuclease-A, protein, kinetics, events
Issue or Number:13
PubMed Central ID:PMC124336
Record Number:CaltechAUTHORS:TEZpnas02
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:987
Deposited By: Tony Diaz
Deposited On:22 Nov 2005
Last Modified:08 Nov 2021 19:06

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