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

Markus Richter 1 Manal Bosnali 1 Linn Carstensen 1 Tobias Seitz 1 Helmut Durchschlag 1 Samuel Blanquart 2 Rainer Merkl 1 Reinhard Sterner 1
1 Institut für Biophysik und physikalische Biochemie
2 BONSAI - Bioinformatics and Sequence Analysis
LIFL - Laboratoire d'Informatique Fondamentale de Lille, Inria Lille - Nord Europe
Abstract : 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.
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https://hal.inria.fr/hal-00755666
Contributor : Samuel Blanquart <>
Submitted on : Wednesday, November 21, 2012 - 4:31:43 PM
Last modification on : Thursday, November 26, 2020 - 11:56:06 AM

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CNRS | INRIA | CRISTAL | CRISTAL-BONSAI | UNIV-LILLE3

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Markus Richter, Manal Bosnali, Linn Carstensen, Tobias Seitz, Helmut Durchschlag, et al.. Computational and experimental evidence for the evolution of a (beta alpha)8-barrel protein from an ancestral quarter-barrel stabilised by disulfide bonds.. Journal of Molecular Biology, Elsevier, 2010, 398 (5), pp.763-73. ⟨10.1016/j.jmb.2010.03.057⟩. ⟨hal-00755666⟩

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