Structural characterisation of the virulence-associated protein VapG from the horse pathogen Rhodococcus equi

Okoko, Tebekeme, Blagova, Elena, Whittingham, Jean, Dover, Lynn and Wilkinson, Anthony (2015) Structural characterisation of the virulence-associated protein VapG from the horse pathogen Rhodococcus equi. Veterinary Microbiology, 179 (1-2). pp. 42-52. ISSN 0378-1135

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Official URL: http://dx.doi.org/10.1016/j.vetmic.2015.01.027

Abstract

Virulence and host range in Rhodococcus equi depends on the variable pathogenicity island of their virulence plasmids. Notable gene products are a family of small secreted virulence-associated proteins (Vaps) that are critical to intramacrophagic proliferation. Equine-adapted strains, which cause severe pyogranulomatous pneumonia in foals, produce a cell-associated VapA that is necessary for virulence, alongside five other secreted homologues. In the absence of biochemical insight, attention has turned to the structures of these proteins to develop a functional hypothesis. Recent studies have described crystal structures for VapD and a truncate of the VapA orthologue of porcine-adapted strains, VapB. Here, we crystallised the full-length VapG and determined its structure by molecular replacement. Electron density corresponding to the N-terminal domain was not visible suggesting that it is disordered. The protein core adopted a compact elliptical, anti-parallel β-barrel fold with β1-β2-β3-β8-β5-β6-β7-β4 topology decorated by a single peripheral α-helix unique to this family. The high glycine content of the protein allows close packing of secondary structural elements. Topologically, the surface has no indentations that indicate a nexus for molecular interactions. The distribution of polar and apolar groups on the surface of VapG is markedly uneven. One-third of the surface is dominated by exposed apolar side-chains, with no ionisable and only four polar side-chains exposed, giving rise to an expansive flat hydrophobic surface. Other surface regions are more polar, especially on or near the α-helix and a belt around the centre of the β-barrel. Possible functional significance of these recent structures is discussed.

Item Type: Article
Uncontrolled Keywords: Virulence-associated protein; Rhodococcus equi; Protein Structure; VapG; VapA
Subjects: B900 Others in Subjects allied to Medicine
C500 Microbiology
C700 Molecular Biology, Biophysics and Biochemistry
D100 Pre-clinical Veterinary Medicine
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: Lynn Dover
Date Deposited: 13 Feb 2015 14:55
Last Modified: 13 May 2017 14:27
URI: http://nrl.northumbria.ac.uk/id/eprint/21399

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