Network mapping among the functional domains of Chikungunya virus nonstructural proteins
Autor(es): Rana Jyoti, Rajasekharan Sreejith, Gulati Sahil, Dudha Namrata, Gupta Amita, Chaudhary Vijay Kumar, Gupta Sanjay
Resumo: Formation of virus specific replicase complex is among the most important steps that determines the fate of viral transcription - replication during Chikungunya virus (CHIKV) infection. In the present study, the authors have computationally generated a 3D structure of CHIKV late replicase complex on the basis of the interactions identified among the domains of CHIKV nonstructural proteins (nsPs) which make up the late replicase complex. The interactions among the domains of CHIKV nsPs were identified using systems such as pull down, protein interaction ELISA, - yeast two-hybrid. The structures of nsPs were generated using I-TASSER - the biological assembly of the replicase complex was determined using ZRANK - RDOCK. A total of 36 interactions among the domains - full length proteins were tested - 12 novel interactions have been identified. These interactions included the homodimerization of nsP1 - nsP4 through their respective C-ter domains; the associations of nsP2 helicase domain - C-ter domain of nsP4 with methyltransferase - membrane binding domains of nsP1; the interaction of nsP2 protease domain with C-ter domain of nsP4; - the interaction of nsP3 macro - alphavirus unique domains with the C-ter domain of nsP1. The novel interactions identified in the current study form a network of organized associations that suggest the spatial arrangement of nsPs in the late replicase complex of CHIKV.
Palavras-Chave: Alphavirus; Protein interactions; Pull down; Replicase complex; Virus replication
Imprenta: Proteins, v. 82, n. 10, p. 2403-2411, 2014
Identificador do objeto digital: 10.1002/prot.24602
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever
Data de publicação: 2014