Document Detail

Computational and experimental evidence for the evolution of a (beta alpha)8-barrel protein from an ancestral quarter-barrel stabilised by disulfide bonds.
MedLine Citation:
PMID:  20363228     Owner:  NLM     Status:  MEDLINE    
The evolution of the prototypical (beta alpha)(8)-barrel protein imidazole glycerol phosphate synthase (HisF) was studied by complementary computational and experimental approaches. The 4-fold symmetry of HisF suggested that its constituting (beta alpha)(2) quarter-barrels have a common evolutionary origin. This conclusion was supported by the computational reconstruction of the HisF sequence of the last common ancestor, which showed that its quarter-barrels were more similar to each other than are those of extant HisF proteins. A comprehensive sequence analysis identified HisF-N1 [corresponding to (beta alpha)(1-2)] as the slowest evolving quarter-barrel. This finding indicated that it is the closest relative of the common (beta alpha)(2) predecessor, which must have been a stable and presumably tetrameric protein. In accordance with this prediction, a recombinantly produced HisF-N1 protein was properly folded and formed a tetramer being stabilised by disulfide bonds. The introduction of a disulfide bond in HisF-C1 [corresponding to (beta alpha)(5-6)] also resulted in the formation of a stable tetramer. The fusion of two identical HisF-N1 quarter-barrels yielded the stable dimeric half-barrel HisF-N1N1. Our findings suggest a two-step evolutionary pathway in which a HisF-N1-like predecessor was duplicated and fused twice to yield HisF. Most likely, the (beta alpha)(2) quarter-barrel and (beta alpha)(4) half-barrel intermediates on this pathway were stabilised by disulfide bonds that became dispensable upon consolidation of the (beta alpha)(8)-barrel.
Markus Richter; Manal Bosnali; Linn Carstensen; Tobias Seitz; Helmut Durchschlag; Samuel Blanquart; Rainer Merkl; Reinhard Sterner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-02
Journal Detail:
Title:  Journal of molecular biology     Volume:  398     ISSN:  1089-8638     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-07     Completed Date:  2010-05-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  763-73     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier Ltd. All rights reserved.
Institute of Biophysics and Physical Biochemistry, University of Regensburg, Universit?tsstrasse 31, D-93053 Regensburg, Germany.
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MeSH Terms
Aminohydrolases / chemistry*,  genetics*,  metabolism
Bacterial Proteins / chemistry*,  genetics*,  metabolism
Computational Biology
Evolution, Molecular*
Models, Molecular
Protein Folding*
Recombinant Proteins / chemistry,  genetics,  metabolism
Thermotoga maritima / enzymology*
Reg. No./Substance:
0/Bacterial Proteins; 0/Disulfides; 0/Recombinant Proteins; EC 3.5.1.-/imidazole glycerol phosphate synthase; EC 3.5.4.-/Aminohydrolases

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