The complement system has evolved to annul pathogens, but its improper regulation is linked with diseases. Efficient regulation of the system is primarily provided by a family of proteins termed regulators of complement activation (RCA). The knowledge of precise structural determinants of RCA proteins critical for imparting the regulatory activities and the molecular events underlying the regulatory processes, nonetheless, is still limited.
View Article and Find Full Text PDFPoxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. One among this array is a homolog of the host complement regulatory proteins that is conserved in various poxviruses including vaccinia (VACV) and variola. The vaccinia virus complement control protein (VCP), which inhibits complement by decaying the classical pathway C3-convertase (decay-accelerating activity), and by supporting inactivation of C3b and C4b by serine protease factor I (cofactor activity), was shown to play a role in viral pathogenesis.
View Article and Find Full Text PDFVaccinia virus encodes a homolog of the human complement regulators named vaccinia virus complement control protein (VCP). It is composed of four contiguous complement control protein (CCP) domains. Previously, VCP has been shown to bind to C3b and C4b and to inactivate the classical and alternative pathway C3 convertases by accelerating the decay of the classical pathway C3 convertase and (to a limited extent) the alternative pathway C3 convertase, as well as by supporting the factor I-mediated inactivation of C3b and C4b (the subunits of C3 convertases).
View Article and Find Full Text PDFRecently it has been shown that kaposica, an immune evasion protein of Kaposi's sarcoma-associated herpesvirus, inactivates complement by acting on C3-convertases by accelerating their decay as well as by acting as a cofactor in factor I-mediated inactivation of their subunits C3b and C4b. Here, we have mapped the functional domains of kaposica. We show that SCRs 1 and 2 (SCRs 1-2) and 1-4 are essential for the classical and alternative pathway C3-convertase decay-accelerating activity (DAA), respectively, while the SCRs 2-3 are required for factor I cofactor activity (CFA) for C3b and C4b.
View Article and Find Full Text PDFThe vaccinia virus complement control protein (VCP) is an immune evasion protein of vaccinia virus. Previously, VCP has been shown to bind and support inactivation of host complement proteins C3b and C4b and to protect the vaccinia virions from antibody-dependent complement-enhanced neutralization. However, the molecular mechanisms involved in the interaction of VCP with its target proteins C3b and C4b have not yet been elucidated.
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