Structure of staphylococcus aureus EsxA suggests a contribution to virulence by action as a transport chaperone and/or adaptor protein

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    Abstract

    Staphylococcus aureus pathogenesis depends on a specialized protein secretion system (ESX-1) that delivers a range of virulence factors to assist infectivity. We report the characterization of two such factors, EsxA and EsxB, small acidic dimeric proteins carrying a distinctive WXG motif. EsxA crystallized in triclinic and monoclinic forms and high-resolution structures were determined. The asymmetric unit of each crystal form is a dimer. The EsxA subunit forms an elongated cylindrical structure created from side-by-side alpha-helices linked with a hairpin bend formed by the WXG motif. Approximately 25% of the solvent accessible surface area of each subunit is involved in interactions, predominantly hydrophobic, with the partner subunit. Secondary-structure predictions suggest that EsxB displays a similar structure. The WXG motif helps to create a shallow cleft at each end of the dimer, forming a short beta-sheet-like feature with an N-terminal segment of the partner subunit. Structural and sequence comparisons, exploiting biological data on related proteins found in Mycobacterium tuberculosis, suggest that this fan-Lily of proteins may contribute to pathogenesis by transporting protein cargo through the ESX-1 system exploiting a C-terminal secretion signal and/or are capable of acting as adaptor proteins to facilitate interactions with host receptor proteins. (C) 2008 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)603-614
    Number of pages12
    JournalJournal of Molecular Biology
    Volume383
    Issue number3
    DOIs
    Publication statusPublished - 14 Nov 2008

    Keywords

    • adaptor protein
    • chaperone
    • helical bundle
    • secretion system
    • virulence factor
    • FIBRONECTIN-BINDING PROTEINS
    • MYCOBACTERIUM-BOVIS BCG
    • T-CELL ANTIGEN
    • ANTIMICROBIAL RESISTANCE
    • ESAT-6-CFP-10 COMPLEX
    • SECRETION SYSTEM
    • DIFFRACTION DATA
    • CALMETTE-GUERIN
    • TUBERCULOSIS
    • ESAT-6

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