Document Detail

Experimental support for the foldability-function tradeoff hypothesis: segregation of the folding nucleus and functional regions in fibroblast growth factor-1.
MedLine Citation:
PMID:  23047594     Owner:  NLM     Status:  MEDLINE    
The acquisition of function is often associated with destabilizing mutations, giving rise to the stability-function tradeoff hypothesis. To test whether function is also accommodated at the expense of foldability, fibroblast growth factor-1 (FGF-1) was subjected to a comprehensive φ-value analysis at each of the 11 turn regions. FGF-1, a β-trefoil fold, represents an excellent model system with which to evaluate the influence of function on foldability: because of its threefold symmetric structure, analysis of FGF-1 allows for direct comparisons between symmetry-related regions of the protein that are associated with function to those that are not; thus, a structural basis for regions of foldability can potentially be identified. The resulting φ-value distribution of FGF-1 is highly polarized, with the majority of positions described as either folded-like or denatured-like in the folding transition state. Regions important for folding are shown to be asymmetrically distributed within the protein architecture; furthermore, regions associated with function (i.e., heparin-binding affinity and receptor-binding affinity) are localized to regions of the protein that fold after barrier crossing (late in the folding pathway). These results provide experimental support for the foldability-function tradeoff hypothesis in the evolution of FGF-1. Notably, the results identify the potential for folding redundancy in symmetric protein architecture with important implications for protein evolution and design.
Liam Longo; Jihun Lee; Michael Blaber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-06
Journal Detail:
Title:  Protein science : a publication of the Protein Society     Volume:  21     ISSN:  1469-896X     ISO Abbreviation:  Protein Sci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-04-29     Revised Date:  2014-01-15    
Medline Journal Info:
Nlm Unique ID:  9211750     Medline TA:  Protein Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1911-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 The Protein Society.
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MeSH Terms
Fibroblast Growth Factor 1 / chemistry*
Models, Molecular
Protein Conformation
Protein Denaturation
Protein Folding*
Reg. No./Substance:
104781-85-3/Fibroblast Growth Factor 1
Comment In:
Protein Sci. 2013 Jul;22(7):869   [PMID:  23804309 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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