Richter, Markus and Bosnali, Manal and Carstensen, Linn and Seitz, Tobias and Durchschlag, Helmut and Blanquart, Samuel and Merkl, Rainer and Sterner, Reinhard (2010) Computational and Experimental Evidence for the Evolution of a (betaalpha)(8)-Barrel Protein from an Ancestral Quarter-Barrel Stabilised by Disulfide Bonds. J Mol Biol 398, pp. 763-773.
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Other URL: http://dx.doi.org/10.1016/j.jmb.2010.03.057
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.
|Date:||7 April 2010|
|Institutions:||Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner > Arbeitsgruppe PD Dr. Rainer Merkl|
|Keywords:||protein evolution; (βα)8-barrel; sequence reconstruction; disulfide bond|
|Subjects:||500 Science > 570 Life sciences|
000 Computer science, information & general works > 004 Computer science
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||19 May 2010 06:41|
|Last Modified:||02 Jul 2010 07:22|