title: A novel mechanism of complement inhibition unmasked by a tick salivary protein that binds to properdin.
abstract: Ixodes scapularis salivary protein 20 (Salp20) is a member of the Ixodes scapularis anti-complement protein-like family of tick salivary proteins that inhibit the alternative complement pathway. In this study, we demonstrate that the target of Salp20 is properdin. Properdin is a natural, positive regulator of the alternative pathway that binds to the C3 convertase, stabilizing the molecule. Salp20 directly bound to and displaced properdin from the C3 convertase. Displacement of properdin accelerated the decay of the C3 convertase, leading to inhibition of the alternative pathway. S20NS is distinct from known decay accelerating factors, such as decay accelerating factor, complement receptor 1, and factor H, which directly interact with either C3b or cleaved factor B.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Tyson
authors.forename: Christopher
authors.initials: C
authors.lastname: Elkins
authors.forename: Aravinda M
authors.initials: AM
authors.lastname: de Silva
mesh_terms: D000818:Animals; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000276:immunology; D006801:Humans; D018884:Ixodes; D011414:Properdin / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
chemical_list: D003169:Complement Inactivator Proteins; C411881:Isac protein, Ixodes scapularis; C455900:Ixolaris protein, Ixodes scapularis; D012471:Salivary Proteins and Peptides; D011414:Properdin; D050577:Complement C3-C5 Convertases