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      Structure of the virulence-associated protein VapD from the intracellular pathogen Rhodococcus equi

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          Abstract

          VapD is one of a set of highly homologous virulence-associated proteins from the multi-host pathogen Rhodococcus equi. The crystal structure reveals an eight-stranded β-barrel with a novel fold and a glycine rich ‘bald’ surface.

          Abstract

          Rhodococcus equi is a multi-host pathogen that infects a range of animals as well as immune-compromised humans. Equine and porcine isolates harbour a virulence plasmid encoding a homologous family of virulence-associated proteins associated with the capacity of R. equi to divert the normal processes of endosomal maturation, enabling bacterial survival and proliferation in alveolar macrophages. To provide a basis for probing the function of the Vap proteins in virulence, the crystal structure of VapD was determined. VapD is a monomer as determined by multi-angle laser light scattering. The structure reveals an elliptical, compact eight-stranded β-barrel with a novel strand topology and pseudo-twofold symmetry, suggesting evolution from an ancestral dimer. Surface-associated octyl-β- d-glucoside molecules may provide clues to function. Circular-dichroism spectroscopic analysis suggests that the β-barrel structure is preceded by a natively disordered region at the N-terminus. Sequence comparisons indicate that the core folds of the other plasmid-encoded virulence-associated proteins from R. equi strains are similar to that of VapD. It is further shown that sequences encoding putative R. equi Vap-like proteins occur in diverse bacterial species. Finally, the functional implications of the structure are discussed in the light of the unique structural features of VapD and its partial structural similarity to other β-barrel proteins.

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          Author and article information

          Journal
          Acta Crystallogr D Biol Crystallogr
          Acta Crystallogr. D Biol. Crystallogr
          Acta Cryst. D
          Acta Crystallographica Section D: Biological Crystallography
          International Union of Crystallography
          0907-4449
          1399-0047
          01 August 2014
          25 July 2014
          25 July 2014
          : 70
          : Pt 8 ( publisher-idID: d140800 )
          : 2139-2151
          Affiliations
          [a ]Structural Biology Laboratory, Department of Chemistry, University of York , Heslington, York YO10 5DD, England
          [b ]UCD School of Biomolecular and Biomedical Science and UCD Conway Institute, University College Dublin , Dublin, Ireland
          [c ]MRC Laboratory of Molecular Biology , Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, England
          Author notes
          Correspondence e-mail: tony.wilkinson@ 123456york.ac.uk
          [‡]

          These authors contributed equally to this work.

          Article
          dz5336 ABCRE6 S1399004714012632
          10.1107/S1399004714012632
          4118825
          25084333
          b78b18f9-7b6b-4c65-98e0-8271d9bf5d1a
          © Whittingham et al. 2014

          This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

          History
          : 07 May 2014
          : 30 May 2014
          Categories
          Research Papers

          Microscopy & Imaging
          virulence factors,bacterial pathogenesis,rhodococcus equi,vapd
          Microscopy & Imaging
          virulence factors, bacterial pathogenesis, rhodococcus equi, vapd

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