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

DOI: 10.1107/S1399004714012632 DOI Help
PMID: 25084333 PMID Help

Authors: Jean L. Whittingham (University of York) , Elena V. Blagova (University of York) , Ciaran E. Finn (University College Dublin) , Haixia Luo (University College Dublin) , Raúl Miranda-Casoluengo (University College Dublin) , Johan Turkenburg (University of York) , Andrew P. Leech (University of York) , Paul Walton (University of York) , Alexey G. Murzin (MRC Laboratory of Molecular Biology) , Wim G. Meijer (University College Dublin) , Anthony Wilkinson (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 70 , PAGES 2139 - 2151

State: Published (Approved)
Published: August 2014
Diamond Proposal Number(s): 7864

Open Access Open Access

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 -barrel with a novel strand topology and pseudo-twofold symmetry, suggesting evolution from an ancestral dimer. Surface-associated octyl--D-glucoside molecules may provide clues to function. Circular-dichroism spectroscopic analysis suggests that the -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 -barrel proteins.

Journal Keywords: Virulence Factors; Bacterial Pathogenesis; Rhodococcus Equi; Vapd.

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 24/09/2014 16:29


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech Veterinary Medicine

Technical Tags:

Diffraction Macromolecular Crystallography (MX)