Projects per year
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 language | English |
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Pages (from-to) | 603-614 |
Number of pages | 12 |
Journal | Journal of Molecular Biology |
Volume | 383 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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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- 2 Finished
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Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)
Fairlamb, A. (Investigator), Ferguson, M. (Investigator) & Frearson, J. (Investigator)
1/01/08 → 31/12/12
Project: Research
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Aref#d: 19401. Structure, specificity and mechanism of biosynthetic enzymes in trypanosomatids and inhibitor discovery of essential microbial functions (Programme Grant)
Hunter, B. (Investigator)
1/11/07 → 31/12/13
Project: Research