Identification of functional domains in kaposica, the complement control protein homolog of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8).
Recently 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. SCR 3 and SCRs 1 and 4, however, contribute to optimal classical pathway DAA and C3b CFA, respectively. Binding data show that SCRs 1-4 and SCRs 1-2 are the smallest structural units required for measuring detectable binding to C3b and C4b, respectively. The heparin-binding site maps to SCR 1.
Mullick
Jayati
J
National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India.
Singh
Akhilesh K
AK
Panse
Yogesh
Y
Yadav
Vivekanand
V
Bernet
John
J
Sahu
Arvind
A
D000595:Amino Acid Sequence; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006493:Heparin; D019288:Herpesvirus 8, Human; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics* / Q000494:pharmacology
C473771:KSHV complement control protein, Herpesvirus 8; D011994:Recombinant Proteins; D014764:Viral Proteins; D003179:Complement C3b; D015935:Complement C4b; D006493:Heparin