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    Molecular architecture and functional analysis of NetB, a pore-forming toxin from Clostridium perfringens

    Savva, Christos G. and Fernandes da Costa, S.P. and Bokori-Brown, M. and Naylor, Claire E. and Cole, Ambrose R. and Moss, David S. and Titball, R.W. and Basak, Ajit K. (2013) Molecular architecture and functional analysis of NetB, a pore-forming toxin from Clostridium perfringens. Journal of Biological Chemistry 288 , pp. 3512-3522. ISSN 0021-9258.

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    Abstract

    NetB is a pore-forming toxin produced by Clostridium perfringens and has been reported to play a major role in the pathogenesis of avian necrotic enteritis, a disease that has emerged due to the removal of antibiotics in animal feedstuffs. Here we present the crystal structure of the pore-form of NetB solved to 3.9Å. The heptameric assembly shares structural homology to the Staphylococcal α-hemolysin. However, the rim domain, a region that is thought to interact with the target cell membrane shows sequence and structural divergence leading to the alteration of a phosphocholine binding pocket found in the staphylococcal toxins. Consistent with the structure we show that NetB does not bind phosphocholine efficiently but instead interacts directly with cholesterol leading to enhanced oligomerisation and pore formation. Finally we have identified conserved and non-conserved amino acid positions within the rim loops that significantly affect binding and toxicity of NetB. These findings present new insights into the mode of action of these pore-forming toxins enabling the design of more effective control measures against necrotic enteritis and providing potential new tools to the field of bionanotechnology.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): Cholesterol, Lipids, Membrane proteins, Toxins, X-ray crystallography, Clostridium perfringens, Necrotic enteritis, Pore forming toxin, alpha hemolysin
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 20 Dec 2012 15:36
    Last Modified: 06 Dec 2016 10:43
    URI: http://eprints.bbk.ac.uk/id/eprint/5921

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