1hr4

Theoretical Model: The protein structure described on this page was determined theoretically, and hence should be interpreted with caution.

MOLECULAR MODEL OF DOMAINS 3 AND 4 OF MEMBRANE COFACTOR PROTEIN (MCP, CD46)

spinqualitylabelsall models 1hr4 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, PDBsum Publication Abstract from PubMed Adherence of group A streptococcus (GAS) to keratinocytes is mediated by an interaction between human CD46 (membrane cofactor protein) with streptococcal cell surface M protein. CD46 belongs to a family of proteins that contain structurally related short consensus repeat (SCR) domains and regulate the activation of the complement components C3b and/or C4b. CD46 possesses four SCR domains and the aim of this study was to characterize their interaction with M protein. Following confirmation of the M6 protein-dependent interaction between GAS and human keratinocytes, we demonstrated that M6 protein binds soluble recombinant CD46 protein and to a CD46 construct containing only SCRs 3 and 4. M6 protein did not bind to soluble recombinant CD46 chimeric proteins that had the third and/or fourth SCR domains replaced with the corresponding domains from another complement regulator, CD55 (decay-accelerating factor). Homology-based molecular modeling of CD46 SCRs 3 and 4 revealed a cluster of positively charged residues between the interface of these SCR domains similar to the verified M protein binding sites on the plasma complement regulators factor H and C4b-binding protein. The presence of excess M6 protein did not inhibit the cofactor activity of CD46 and the presence of excess C3b did not inhibit the ability of CD46 to bind M6 protein by ELISA. In conclusion, 1) adherence of M6 GAS to keratinocytes is M protein dependent and 2) a major M protein binding site is located within SCRs 3 and 4, probably at the interface of these two domains, at a site distinct from the C3b-binding and cofactor site of CD46. Identification of the streptococcal M protein binding site on membrane cofactor protein (CD46).,Giannakis E, Jokiranta TS, Ormsby RJ, Duthy TG, Male DA, Christiansen D, Fischetti VA, Bagley C, Loveland BE, Gordon DL J Immunol. 2002 May 1;168(9):4585-92. PMID:11971006 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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