Atomic-Level Structure Characterization of an Ultrafast Folding Mini-Protein Denatured State

Atomic-level analyses of non-native protein ensembles constitute an important aspect of protein folding studies to reach a more complete understanding of how proteins attain their native form exhibiting biological activi
Atomic-level analyses of non-native protein ensembles constitute an important aspect of protein folding studies to reach a more complete understanding of how proteins attain their native form exhibiting biological activity. Previously, formation of hydrophobic clusters in the 6 M urea-denatured state of an ultrafast folding mini-protein known as TC5b from both photo-CIDNP NOE transfer studies and FCS measurements was observed. Here, we elucidate the structural properties of this mini-protein denatured in 6 M urea performing 15N NMR relaxation studies together with a thorough NOE analysis. Even though our results demonstrate that no elements of secondary structure persist in the denatured state, the heterogeneous distribution of R2 rate constants together with observing pronounced heteronuclear NOEs along the peptide backbone reveals specific regions of urea-denatured TC5b exhibiting a high degree of structural rigidity more frequently observed for native proteins. The data are complemented with studies on two TC5b point mutants to verify the importance of hydrophobic interactions for fast folding. Our results corroborate earlier findings of a hydrophobic cluster present in urea-denatured TC5b comprising both native and non-native contacts underscoring their importance for ultra rapid folding. The data assist in finding ways of interpreting the effects of pre-existing native and/or non-native interactions on the ultrafast folding of proteins; a fact, which might have to be considered when defining the starting conditions for molecular dynamics simulation studies of protein folding.
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Metadaten
Author:Per Rogne, Przemysław Ozdowy, Christian Richter, Krishna Saxena, Harald Schwalbe, Lars T. Kuhn
URN:urn:nbn:de:hebis:30:3-250023
DOI:http://dx.doi.org/10.1371/journal.pone.0041301
ISSN:1932-6203
Parent Title (English):Plos one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Advisor:Marius Luta
Document Type:Article
Language:English
Date of Publication (online):2012/07/27
Date of first Publication:2012/07/27
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/08/13
Volume:7
Issue:7: e41301
Pagenumber:13
First Page:1
Last Page:13
Institutes:Biochemie und Chemie
Dewey Decimal Classification:540 Chemie und zugeordnete Wissenschaften
570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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