title: Crystallization of human complement component C3b in the presence of a staphylococcal complement-inhibitor protein (SCIN).
abstract: Staphylococcus aureus secretes a number of small proteins that effectively attenuate the human innate immune response. Among these, the staphylococcal complement-inhibitor protein (SCIN) disrupts the function of the complement component 3 (C3) convertase that is initiated through either the classical or the alternative pathway and thereby prevents amplification of the complement response on the bacterial surface. Recent studies have shown that SCIN may affect the activities of the C3 convertase by binding in an equimolar fashion to C3b, which is itself an integral although non-enzymatic component of the convertase. In order to better understand the nature of the C3b-SCIN interaction, the hanging-drop vapor-diffusion technique was used to crystallize human C3b in the presence of a recombinant form of SCIN. These crystals diffracted synchrotron X-rays to approximately 6 A Bragg spacing and grew in a primitive tetragonal space group (P4(1)2(1)2 or P4(3)2(1)2; unit-cell parameters a = b = 128.03, c = 468.59 A). Cell-content analysis of these crystals was consistent with the presence of either two 1:1 complexes or a single 2:2 assembly in the asymmetric unit, both of which correspond to a solvent content of 51.9%. By making use of these crystals, solution of the C3b-SCIN structure should further our understanding of complement inhibition and immune evasion by this pathogen.
authors.affiliation: University of Missouri-Kansas City, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Garcia
authors.forename: Apostolia
authors.initials: A
authors.lastname: Tzekou
authors.forename: Kasra X
authors.initials: KX
authors.lastname: Ramyar
authors.forename: William J
authors.initials: WJ
authors.lastname: McWhorter
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Brian V
authors.initials: BV
authors.lastname: Geisbrecht
mesh_terms: D003179:Complement C3b / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D003180:Complement C3b Inactivator Proteins; D003179:Complement C3b