How viral proteins bind short linear motifs and intrinsically disordered domains

Abstract

Abstract Viruses are the obligate intracellular parasites that exploit the host cellular machinery to replicate their genome. During the viral life cycle viruses manipulate the host cell through interactions with host proteins. Many of these protein–protein interactions are mediated through the recognition of host globular domains by short linear motifs (SLiMs), or longer intrinsically disordered domains (IDD), in the disordered regions of viral proteins. However, viruses also employ their own globular domains for binding to SLiMs and IDDs present in host proteins or virus proteins. In this review, we focus on the different strategies adopted by viruses to utilize proteins or protein domains for binding to the disordered regions of human or/and viral ligands. With a set of examples, we describe viral domains that bind human SLiMs. We also provide examples of viral proteins that bind to SLiMs, or IDDs, of viral proteins as a part of complex assembly and regulation of protein functions. The protein–protein interactions are often crucial for viral replication, and may thus offer possibilities for innovative inhibitor design.