EVOLUTION AND FUNCTION OF DISORDERED REGIONS AND LINEAR MOTIFS IN VIRAL PROTEOMES

CHEMES L.B.

Kosice

Conferencia; Conferencia NGP Net: "Action on Intrinsically Disordered Proteins".; 2017

NGP Network COST

Linear motifs are key elements of regulatory protein interaction networks. Viruses take advantage of this by evolving linear motifs (LMs) that hijack and disrupt the host network. Therefore, identifying relevant linear motifs and their binding strength is central to understanding host regulation and viral pathogenesis. However, the degenerate nature of linear motifs makes their identification challenging. Moreover, the identification of disordered domains and flexible regions within folded domains still remains a challenge and is an essential step for defining regions where functional LMs are located. First, we will discuss how the sequence evolution of Retinoblastoma (Rb) binding motifs reveals fine-tuning of binding affinity that establishes the ranking of binding for host and viral motifs. We also present an example where a single viral protein uses several binding motifs for achieving high affinity Rb-association. Secondly, we present a strategy for the identification of intrinsically disordered regions (IDRs) in Flavivirus proteomes. Here, a combined sequence and structural analysis reveals the presence of multiple flexible regions where functional LMs could be located, despite the low average levels of disorder in this viral family. Evolutionary analysis reveals strong conservation of disorder within the Flavivirus family, and also group-specific IDR regions.