Structural bioinformatics insights into the CARD-CARD interaction mediated by the mitochondrial antiviral-signaling protein of black carp.

Abstract

The innate immune system offers the first line of defense against invading microbial pathogens through the recognition of conserved pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). The host innate immune system through PRRs, the sensors for PAMPs, induces the production of cytokines. Among different families of PRRs, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and its mitochondrial adaptor ie, the mitochondrial antiviral-signaling (MAVS) protein, are crucial for RLR-triggered interferon (IFN) antiviral immunity. Recent studies have shownthat the N-terminal caspase recruitment domain (CARD) and transmembrane domain playa pivotal role in oligomerization of black carp MAVS (BcMAVS), crucial for the host innate immune response against viral invasion. In this study, we have used molecular modeling, docking, and molecular dynamics (MD) simulation approaches to shed molecular insights into the oligomerization mechanism of BcMAVSCARD . MD simulation and interaction analysis portrayed that the type-I surface patches of BcMAVS CARD makethe major contributionto the interaction. Moreover, the evidence from surface patches and critical residues involved in the said interaction is found to be similar tothat of the human counterpart and requires further investigation for legitimacy. Altogether, our study provided crucial information on oligomerization of BcMAVS CARDs and might be helpful for clarifying the innate immune response against pathogens and downstream signaling in fishes.