title: Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi' domain 7 of factor H: a molecular modeling study.
abstract: Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or 'sushi' domains of about 60 amino acids each, is a regulator of the complement system. The complement-regulatory functions of factor H are targeted by its binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20. Recently, the SCR 7 heparin-binding site was shown to be co-localized with the Streptococcus Group A M protein binding site on factor H (T.K. Blackmore et al., Infect. Immun. 66, 1427 (1998)). Using sequence analysis of all heparin-binding domains of factor H and its closest homologues, molecular modeling of SCRs 6 and 7, and surface electrostatic potential studies, the residues implicated in heparin/sialic acid binding to SCR 7 have been localized to four regions of sequence space containing stretches of basic as well as histidine residues. The heparin-binding site is spatially compact and lies near the interface between SCRs 6 and 7, with residues in the interdomain linker playing a significant role.
authors.affiliation: Australian Genomic Information Centre, University of Sydney, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ranganathan
authors.forename: D A
authors.initials: DA
authors.lastname: Male
authors.forename: R J
authors.initials: RJ
authors.lastname: Ormsby
authors.forename: E
authors.initials: E
authors.lastname: Giannakis
authors.forename: D L
authors.initials: DL
authors.lastname: Gordon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017242:Complement Factor H / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D016208:Databases, Factual; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D055672:Static Electricity
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H; D006493:Heparin; D019158:N-Acetylneuraminic Acid