Signalling from disordered proteins

Abstract

The discovery that a disordered protein can transmit signals between two binding sites calls into question the idea that communication within proteins requires a specific structural pathway linking such sites. See Letter p.390 Cellular function relies on intricate signalling networks incorporating protein signalling hubs that interact with several partners in order to modulate multiple downstream signals. This study of one such hub, the adenovirus early region 1A (E1A) oncoprotein, uses novel single molecule FRET measurements to overcome aggregation problems and to directly probe the allosteric interactions of E1A with two key partners. The results reveal a striking cooperativity modulation, regulated by multiple interactions and availability of E1A interaction motifs. Such a modulation of allosteric interactions may be a common feature of intrinsically disordered hub proteins.