4bik | pdb_00004bik

Structure of a disulfide locked mutant of Intermedilysin with human CD59

spinqualitylabelsall models 4bik, resolution 3.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bik is a 4 chain structure with sequence from Atcc 27335 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [CD59_HUMAN] Defects in CD59 are the cause of CD59 deficiency (CD59D) [MIM:612300]. Function [CD59_HUMAN] Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase. The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit MAC assembly on cell membranes. Publication Abstract from PubMed Pore-forming proteins containing the structurally conserved membrane attack complex/perforin fold play an important role in immunity and host-pathogen interactions. Intermedilysin (ILY) is an archetypal member of a cholesterol-dependent cytolysin subclass that hijacks the complement receptor CD59 to make cytotoxic pores in human cells. ILY directly competes for the membrane attack complex binding site on CD59, rendering cells susceptible to complement lysis. To understand how these bacterial pores form in lipid bilayers and the role CD59 plays in complement regulation, we determined the crystal structure of human CD59 bound to ILY. Here, we show the ILY-CD59 complex at 3.5 A resolution and identify two interfaces mediating this host-pathogen interaction. An ILY-derived peptide based on the binding site inhibits pore formation in a CD59-containing liposome model system. These data provide insight into how CD59 coordinates ILY monomers, nucleating an early prepore state, and suggest a potential mechanism of inhibition for the complement terminal pathway. Structural Basis for Recognition of the Pore-Forming Toxin Intermedilysin by Human Complement Receptor CD59.,Johnson S, Brooks NJ, Smith RA, Lea SM, Bubeck D Cell Rep. 2013 May 30;3(5):1369-77. doi: 10.1016/j.celrep.2013.04.029. Epub 2013 , May 9. PMID:23665225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also CD59

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