5i0q

Structure of human C4b-binding protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of mutant group A Streptococcus M2 (K65A, N66A) protein

spinqualitylabelsall models 5i0q, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5i0q is a 2 chain structure with sequence from Homo sapiens and Streptococcus pyogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.293Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function M21_STRPY This protein is one of the different antigenic serotypes of protein M. Protein M is closely associated with virulence of the bacterium and can render the organism resistant to phagocytosis. Publication Abstract from PubMed No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently approximately 90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant 'reading head' in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M-C4BP interaction, and also inform a path towards vaccine design. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein.,Buffalo CZ, Bahn-Suh AJ, Hirakis SP, Biswas T, Amaro RE, Nizet V, Ghosh P Nat Microbiol. 2016 Sep 5:16155. doi: 10.1038/nmicrobiol.2016.155. PMID:27595425 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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