Title :

Computational and experimental evidence for the evolution of a (beta alpha)8-barrel protein from an ancestral quarter-barrel stabilised by disulfide bonds.

Author(s) :

Richter, Markus [Auteur]
Bosnali, Manal [Auteur]
Carstensen, Linn [Auteur]
Seitz, Tobias [Auteur]
Durchschlag, Helmut [Auteur]
Blanquart, Samuel [Auteur]
Bioinformatics and Sequence Analysis [BONSAI]
Merkl, Rainer [Auteur]
Sterner, Reinhard [Auteur]

Journal title :

Journal of Molecular Biology

Pages :

763-73

Publisher :

Elsevier

Publication date :

2010-05-21

ISSN :

0022-2836

HAL domain(s) :

Sciences du Vivant [q-bio]/Bio-Informatique, Biologie Systémique [q-bio.QM]
Informatique [cs]/Bio-informatique [q-bio.QM]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189

Source :

Harvested from HAL