5iuc

Crystal structure of the GspB siglec domain with sialyl T antigen bound

spinqualitylabelsall models 5iuc, resolution 1.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5iuc is a 2 chain structure. This structure supersedes the now removed PDB entries 4i8e and 3qd1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A2G, GAL, MG, SIA Related: 3qc5, 3qc6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [GSPB_STRGN] Plays a role in virulence and host-pathogen interactions. Mediates binding to human platelets via interaction with the human cell surface glycoprotein GP1BA. Publication Abstract from PubMed GspB is a serine-rich repeat (SRR) adhesin of Streptococcus gordonii that mediates binding of this organism to human platelets via its interaction with sialyl-T antigen on the receptor GPIbalpha. This interaction appears to be a major virulence determinant in the pathogenesis of infective endocarditis. To address the mechanism by which GspB recognizes its carbohydrate ligand, we determined the high-resolution x-ray crystal structure of the GspB binding region (GspB(BR)), both alone and in complex with a disaccharide precursor to sialyl-T antigen. Analysis of the GspB(BR) structure revealed that it is comprised of three independently folded subdomains or modules: 1) an Ig-fold resembling a CnaA domain from prokaryotic pathogens; 2) a second Ig-fold resembling the binding region of mammalian Siglecs; 3) a subdomain of unique fold. The disaccharide was found to bind in a pocket within the Siglec subdomain, but at a site distinct from that observed in mammalian Siglecs. Confirming the biological relevance of this binding pocket, we produced three isogenic variants of S. gordonii, each containing a single point mutation of a residue lining this binding pocket. These variants have reduced binding to carbohydrates of GPIbalpha. Further examination of purified GspB(BR)-R484E showed reduced binding to sialyl-T antigen while S. gordonii harboring this mutation did not efficiently bind platelets and showed a significant reduction in virulence, as measured by an animal model of endocarditis. Analysis of other SRR proteins revealed that the predicted binding regions of these adhesins also had a modular organization, with those known to bind carbohydrate receptors having modules homologous to the Siglec and Unique subdomains of GspB(BR). This suggests that the binding specificity of the SRR family of adhesins is determined by the type and organization of discrete modules within the binding domains, which may affect the tropism of organisms for different tissues. A Structural Model for Binding of the Serine-Rich Repeat Adhesin GspB to Host Carbohydrate Receptors.,Pyburn TM, Bensing BA, Xiong YQ, Melancon BJ, Tomasiak TM, Ward NJ, Yankovskaya V, Oliver KM, Cecchini G, Sulikowski GA, Tyska MJ, Sullam PM, Iverson TM PLoS Pathog. 2011 Jul;7(7):e1002112. Epub 2011 Jul 7. PMID:21765814 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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