Reza , M.J. and Kamble , A. and Ahmad , M. and Krishnasastry , M.V. and Sahu, A. (2013) Dissection of Functional Sites in Herpesvirus Saimiri Complement Control Protein Homolog. Journal of Virology, 87 (1). 282-295 . ISSN Journal of Virology p. 282–295 January 2013 Volume 87 Number 1

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Abstract

Herpesvirus saimiri is known to encode a homolog of human complement regulators named complement control protein homolog (CCPH). We have previously reported that this virally encoded inhibitor effectively inactivates complement by supporting factor I-mediated inactivation of complement proteins C3b and C4b (termed cofactor activity), as well as by accelerating the irreversible decay of the classical/lectin and alternative pathway C3 convertases (termed decay-accelerating activity). To fine map its functional sites, in the present study, we have generated a homology model of CCPH and performed substitution mutagenesis of its conserved residues. Functional analyses of 24 substitution mutants of CCPH indicated that (i) amino acids R118 and F144 play a critical role in imparting C3b and C4b cofactor activities, (ii) amino acids R35, K142, and K191 are required for efficient decay of the C3 convertases, (iii) positively charged amino acids of the linker regions, which are dubbed to be critical for functioning in other complement regulators, are not crucial for its function, and (iv) S100K and G110D mutations substantially enhance its decay-accelerating activities without affecting the cofactor activities. Overall, our data point out that ionic interactions form a major component of the binding interface between CCPH and its interacting partners.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	10 Apr 2015 11:06
Last Modified:	02 Jul 2015 10:42
URI:	http://nccs.sciencecentral.in/id/eprint/40

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