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bioRxiv · 10.1101/226605

Presence of WH2 like domain in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking

Dutta, P.·A S, J.·Mazumder, M.·Dileep, D.·Gourinath, S.·Mukhopadhyay, A. K.·Maiti, S.
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Abstract

Type VI secretion systems (T6SS) plays a crucial role in Vibrio cholerae mediated pathogenicity and predation. Tip of T6SS is homologous to gp27/gp5 complex or tail spike of T4 bacteriophage. VgrG-1 of V. cholerae T6SS is unusual among other VgrG because its effector domain is trans-located into the cytosol of eukaryotic cells with an additional actin cross-linking domain (ACD) at its C terminal end. ACD of VgrG-1 (VgrG-1-ACD) causes T6SS dependent host cell cytotoxicity through actin cytoskeleton disruption to prevent bacterial engulfment by macrophages. ACD mediated actin cross-linking promotes survival of the bacteria in the small intestine of humans, along with other virulence factors; establishes successful infection with the onset of diarrhoea in humans. Our studies demonstrated VgrG-1-ACD can bind to actin besides actin cross-linking activity. Computational analysis of ACD revealed the presence of WH2 domain through which it binds actin. Mutations in WH2 domain lead to loss of actin binding in vitro. VgrG-1-ACD having the mutated WH2 domain cannot cross-link actin efficiently in vitro and manifests less actin cytoskeleton disruption when transfected in HeLa cells.\n\nSummary statementActin cross-linking (ACD) domain of VgrG-1 toxin of Type VI secretion in Vibrio cholera has WASP Homology domain 2 (WH2) domain. ACD interact with actin through WH2 domain, WH2 is essential for ACD mediated cross-linking and disruption of actin cytoskeleton in the host cell.

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Dutta, P., A S, J., Mazumder, M., Dileep, D., Gourinath, S., Mukhopadhyay, A. K., Maiti, S.. 2017-11-29. Presence of WH2 like domain in VgrG-1 toxin of Vibrio cholerae reveals the molecular mechanism of actin cross-linking. https://doi.org/10.1101/226605

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