2qej

From Proteopedia

Revision as of 11:35, 23 January 2008

Crystal structure of a Staphylococcus aureus protein (SSL7) in complex with Fc of human IgA1

Overview

Infection by Staphylococcus aureus can result in severe conditions such as, septicemia, toxic shock, pneumonia, and endocarditis with antibiotic, resistance and persistent nasal carriage in normal individuals being key, drivers of the medical impact of this virulent pathogen. In both virulent, infection and nasal colonization, S. aureus encounters the host immune, system and produces a wide array of factors that frustrate host immunity., One in particular, the prototypical staphylococcal superantigen-like, protein SSL7, potently binds IgA and C5, thereby inhibiting immune, responses dependent on these major immune mediators. We report here the, three-dimensional structure of the complex of SSL7 with Fc of human IgA1, at 3.2 A resolution. Two SSL7 molecules interact with the Fc (one per, heavy chain) primarily at the junction between the Calpha2 and Calpha3, domains. The binding site on each IgA chain is extensive, with SSL7, shielding most of the lateral surface of the Calpha3 domain. However, the, SSL7 molecules are positioned such that they should allow binding to, secretory IgA. The key IgA residues interacting with SSL7 are also bound, by the leukocyte IgA receptor, FcalphaRI (CD89), thereby explaining how, SSL7 potently inhibits IgA-dependent cellular effector functions mediated, by FcalphaRI, such as phagocytosis, degranulation, and respiratory burst., Thus, the ability of S. aureus to subvert IgA-mediated immunity is likely, to facilitate survival in mucosal environments such as the nasal passage, and may contribute to systemic infections.

About this Structure

2QEJ is a Single protein structure of sequence from Homo sapiens and Staphylococcus aureus with and as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1., Ramsland PA, Willoughby N, Trist HM, Farrugia W, Hogarth PM, Fraser JD, Wines BD, Proc Natl Acad Sci U S A. 2007 Sep 11;. PMID:17848512

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