Ojha H, , H. and Mahajan G, , G. and Mande SC, , S.C. and Sahu A, A. (2016) In silico identification of CCP sequence motifs allow identification of novel complement regulators. Immunobiology , 221 (10). p. 1166.

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Abstract

Activation of the complement system on host cells is regulated primarily by a family of proteins termed as regulators of complement activation (RCA). A characteristic feature of the RCA family of proteins is the presence of repeating complement control protein (CCP) domains. Recent advances in genome sequencing resulted in availability of a large pool of sequences encoding CCP domain-containing proteins. However, their functional annotation could not be performed as CCP domains are not exclusive to RCA family (e.g., also present in proteins involved in complement activation, cell adhesion, coagulation, neurotransmission, cytokine signalling and blood clotting) and not all RCA family members are capable of regulating complement (e.g., Complement Receptor 2). In the present study, we therefore, sought to identify whether RCA proteins with complement regulatory function contain any sequence motif indicative of their function. In silico analysis of three N-terminal CCP domains of mammalian and viral RCA proteins resulted in identification of five motifs. These motifs are present in a specific order and are conserved spatially. Phylum-wide analysis of genomes for the presence of proteins with these motifs showed that they are present in CCP domain-containing proteins of a wide variety of organisms ranging from mammalia to nematoda, which included annotated and unannotated proteins for complement regulatory function. Thus, this approach seems to have broad-range sensitivity. To experimentally validate whether these motifs are indeed critical for complement regulatory activities, we performed functional characterization of human SVEP1 (Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1)/Polydom expressed in placenta, which contains these motifs, but has not been characterised to have complement regulatory function. The protein displayed the complement regulatory activities. We therefore propose that the sequence motifs we have identified are capable of distinguishing between regulatory and non-regulatory CCP domains and thus are apt for identifying new complement regulatory proteins in a continually expanding dataset of CCP containing proteins.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	29 Nov 2017 07:25
Last Modified:	29 Nov 2017 07:25
URI:	http://nccs.sciencecentral.in/id/eprint/474

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