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PDBsum entry 2qej
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Immune system
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PDB id
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2qej
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References listed in PDB file
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Key reference
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Title
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Structural basis for evasion of iga immunity by staphylococcus aureus revealed in the complex of ssl7 with fc of human iga1.
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Authors
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P.A.Ramsland,
N.Willoughby,
H.M.Trist,
W.Farrugia,
P.M.Hogarth,
J.D.Fraser,
B.D.Wines.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
15051-15056.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Fig. 1. Crystal structure of SSL7 bound to Fc of human
IgA1. (A) Ribbons-style representation with the IgA-Fc homodimer
(heavy chains, magenta and cyan; carbohydrates, orange CPK
spheres) and the two SSL7 molecules (yellow and red) with
secondary structure displayed. (B) Solvent-accessible surface
view of the SSL7 complex with IgA-Fc.
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Figure 3.
Fig. 3. Surface views of binding regions on SSL7 and the Fc
of human IgA1. (A) Residues at the interface (  4 Å)
are mapped to the molecular surfaces of the Fc (chain A, cyan;
chain B, orange) and SSL7 (chain D, yellow) for one complex of
SSL7 and the Fc. (B) Side view of the interaction between SSL7
and the Fc.
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