1dee
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CRYSTAL STRUCTURE AT 2.7A RESOLUTION OF A COMPLEX BETWEEN A STAPHYLOCOCCUS AUREUS DOMAIN AND A FAB FRAGMENT OF A HUMAN IGM ANTIBODY
OverviewOverview
Staphylococcus aureus produces a virulence factor, protein A (SpA), that, contains five homologous Ig-binding domains. The interactions of SpA with, the Fab region of membrane-anchored Igs can stimulate a large fraction of, B cells, contributing to lymphocyte clonal selection. To understand the, molecular basis for this activity, we have solved the crystal structure of, the complex between domain D of SpA and the Fab fragment of a human IgM, antibody to 2.7-A resolution. In the complex, helices II and III of domain, D interact with the variable region of the Fab heavy chain (V(H)) through, framework residues, without the involvement of the hypervariable regions, implicated in antigen recognition. The contact residues are highly, conserved in human V(H)3 antibodies but not in other families. The contact, residues from domain D also are conserved among all SpA Ig-binding, domains, suggesting that each could bind in a similar manner. Features of, this interaction parallel those reported for staphylococcal enterotoxins, that are superantigens for many T cells. The structural homology between, Ig V(H) regions and the T-cell receptor V(beta) regions facilitates their, comparison, and both types of interactions involve lymphocyte receptor, surface remote from the antigen binding site. However, T-cell, superantigens reportedly interact through hydrogen bonds with T-cell, receptor V(beta) backbone atoms in a primary sequence-independent manner, whereas SpA relies on a sequence-restricted conformational binding with, residue side chains, suggesting that this common bacterial pathogen has, adopted distinct molecular recognition strategies for affecting large sets, of B and T lymphocytes.
About this StructureAbout this Structure
1DEE is a Single protein structure of sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity., Graille M, Stura EA, Corper AL, Sutton BJ, Taussig MJ, Charbonnier JB, Silverman GJ, Proc Natl Acad Sci U S A. 2000 May 9;97(10):5399-404. PMID:10805799
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