Localization of functional sites in the viral complement inhibitor KCP

• Kaposi's sarcoma-associated herpes virus (KSHV) encodes a complement inhibitor named KSHV complement control protein (KCP). We have previously shown that KCP inhibits the human complement system by disrupting the C3 convertase of complement. KCP can accelerate the decay of the classical C3 convertase and it can act as a cofactor for factor I (R), which then cleaves and inactivates C4b or C3b (in the classical and alternative convertase, respectively). The aim of this study was to 1) delineate the sites on KCP responsible for complement inhibition 2) study the binding of KCP to heparin and the surface of cells. We constructed a 3D model of the four CCP domains KCP by homology based modeling, which served as basis for site directed mutagenesis. A patch of positively charged amino acids in CCPI, stretching into CCP2 as well as a positive and a negative patch in the region between CCP2-3 were the most functionally important sites. KCP binds to heparin and the surface of cells via a site in CCPI.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

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