5hyu

Structure of human C4b-binding protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of group A Streptococcus M2 proteinStructure of human C4b-binding protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of group A Streptococcus M2 protein

Structural highlights 5hyu is a 2 chain structure with sequence from "micrococcus_scarlatinae"_klein_1884 "micrococcus scarlatinae" klein 1884 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5hyp, 5hyt, 5hzp, 5i0q Gene: emmL2.1 ("Micrococcus scarlatinae" Klein 1884), C4BPA, C4BP (HUMAN) 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. [C4BPA_HUMAN] Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. Alpha chain binds C4b. It interacts also with anticoagulant protein S and with serum amyloid P component. 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.

spinqualitylabelsall models 5hyu, resolution 2.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image