title: Attribution of the various inhibitory actions of the streptococcal inhibitor of complement (SIC) to regions within the molecule.
abstract: Some strains of Streptococcus pyogenes secrete a virulence factor called the streptococcal inhibitor of complement (SIC) function. SIC is a polyfunctional protein that interacts with a number of host proteins and peptides, especially with those that are involved in host defense systems. In addition to inhibiting the complement-mediated lysis of cells, SIC inhibits lysozyme, secretory leukocyte proteinase inhibitor, and beta-defensins. SIC also binds to proteins associated with the cytoskeleton and thereby may cause cytoskeletal derangement. The SIC molecule has three distinct structural domains constituting the N-proximal short repeat region (SRR), the central long repeat region (LRR), and the C-proximal proline-rich region (PRR). To map various functions to the structural domains, we have analyzed recombinant subclones expressing various parts of SIC and elastase-generated discrete fragments of SIC for binding to various ligands and for determining their biological properties. The results demonstrate the following. (a) SRR alone was sufficient to confer inhibition of complement function. (b) Anti-defensin and anti-lysozyme activities were mapped to the SRR plus LRR. (c) The LRR plus PRR harbored ezrin binding activity.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Binks
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fernie-King
authors.forename: David J
authors.initials: DJ
authors.lastname: Seilly
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lachmann
authors.forename: Kadaba S
authors.initials: KS
authors.lastname: Sriprakash
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D002645:Chickens; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D003598:Cytoskeletal Proteins; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D009113:Muramidase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D023083:beta-Defensins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099149:Ezrin
chemical_list: D001426:Bacterial Proteins; D003169:Complement Inactivator Proteins; D003598:Cytoskeletal Proteins; D009113:Muramidase; D010446:Peptide Fragments; D010750:Phosphoproteins; D011994:Recombinant Proteins; D023083:beta-Defensins; D000099149:Ezrin; C422950:DEFB103A protein, human; C097739:SIC protein, Streptococcus