title: Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation.
abstract: Complement factor B is a 90 kDa protein consisting of three domains: a three-module complement control protein, a von Willebrand factor A domain, and a C-terminal serine protease (SP) domain that adopts a default inactive (zymogen) conformation. The interaction between factor B and pathogen-bound C3b is mediated by its A domain, triggering a conformational change in factor B that ultimately creates the "C3 convertase" of the alternative complement pathway. We report the crystal structure of the A domain from factor B and show that it contains an integrin-like MIDAS motif that adopts the "open" conformation typical of integrin-ligand complexes, with an acidic residue (provided by a fortuitous crystal contact) completing the coordination of the metal ion. Modeling studies indicate that the factor B A domain can also adopt the closed conformation, supporting the hypothesis that an "integrin-like switch" is conserved in complement proteins and perhaps in 60 other A domains found within the human proteome.
authors.affiliation: The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Ananyo A
authors.initials: AA
authors.lastname: Bhattacharya
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lupher
authors.forename: Donald E
authors.initials: DE
authors.lastname: Staunton
authors.forename: Robert C
authors.initials: RC
authors.lastname: Liddington
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003175:Complement C2 / Q000235:genetics; D011415:Complement Factor B / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D016023:Integrins / Q000235:genetics; D008024:Ligands; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D003175:Complement C2; D016023:Integrins; D008024:Ligands; C068563:complement C2, C allele protein; D011415:Complement Factor B