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

DOI: 10.1016/j.vetmic.2015.01.027 DOI Help
PMID: 25746683 PMID Help

Authors: Tebekeme Okoko (Department of Applied Sciences, Northumbria University) , Elena Blagova (Structural Biology Laboratory, University of York) , Jean L. Whittingham (Structural Biology Laboratory, University of York) , Lynn G. Dover (Department of Applied Sciences, Northumbria University) , Anthony Wilkinson (Structural Biology Laboratory, University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Veterinary Microbiology , VOL 179 , PAGES 42 - 52

State: Published (Approved)
Published: August 2015

Open Access Open Access

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.

Journal Keywords: Nce-Associated Protein; Rhodococcus Equi; Protein Structure; Vapg; Vapa

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography