Intrinsic disorder in proteins involved in the innate antiviral immunity: another flexible side of a molecular arms race.

ABSTRACT

We present a comprehensive bioinformatics analysis of the abundance and roles of intrinsic disorder in human proteins involved in the antiviral innate immune response. The commonness of intrinsic disorder and disorder-based binding sites is evaluated in 840 human antiviral proteins and proteins associated with innate immune response and defense response to virus. Among the mechanisms engaged in the innate immunity to viral infection are three receptor-based pathways activated by the specific recognition of various virus-associated patterns by several retinoic acid-inducible gene I-like receptors, toll-like receptors, and nucleotide oligomerization domain-like receptors. These modules are tightly regulated and intimately interconnected being jointly controlled via a complex set of protein-protein interactions. Focused analysis of the major players involved in these three pathways is performed to illustrate the roles of protein intrinsic disorder in controlling and regulating the innate antiviral immunity. We mapped the disorder into an integrated network of receptor-based pathways of human innate immunity to virus infection and demonstrate that proteins involved in regulation and execution of these innate immunity pathways possess substantial amount of intrinsic disorder. Disordered regions are engaged in a number of crucial functions, such as protein-protein interactions and interactions with other partners including nucleic acids and other ligands, and are enriched in posttranslational modification sites. Therefore, host cells use numerous advantages of intrinsically disordered proteins and regions to fight flexible invaders and viruses and to successfully overcome the viral invasion.