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A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin¹

Katharine R. Tyson^*, Christopher Elkins and Aravinda M. de Silva^2,*

^* Department of Microbiology and Immunology and Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant U01 AI058263.

² Address correspondence and reprint requests to Dr. Aravinda M. de Silva, Department of Microbiology and Immunology, University of North Carolina, CB No. 7290 Chapel Hill, NC 27599. E-mail address: desilva{at}med.unc.edu

³ Abbreviations used in this paper: Isac, I. scapularis anti-complement protein; Irac, I. ricinus anti-complement protein; ILP, Isac-like protein; NHS, normal human serum; Salp20, salivary protein 20; CAT, chloramphenicol acetyltransferase; AP, alkaline phosphatase; fB, factor B; Bb, cleaved factor B; fH, factor H; fI, factor I; fD, factor D; C3bP, C3b-properdin complex; SGE, salivary gland extract; CVF, cobra venom factor; TSR, thrombospondin type I repeat.

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