Intrinsically disordered proteins (IDPs) challenge the traditional structure–function paradigm by lacking stable three-dimensional folds while playing essential intracellular roles. In this talk, I will describe our efforts to understand how sequence-encoded interactions in IDPs give rise to ordered conformational ensembles, collective behavior, and function across molecular, mesoscopic, and cellular scales. At the molecular scale, we show that disordered sequences encode nonrandom structural organization through transient and heterogeneous interactions, which can regulate transcriptional activity. At the mesoscopic scale, we investigate the relationship between liquid–liquid phase separation and aggregation, showing that these processes can be decoupled and selectively modulated. At the cellular scale, we demonstrate that phase separation can be harnessed as a systems-level control mechanism to buffer gene expression against growth-mediated dilution. Together, these studies suggest that disorder at the monomeric level can be highly organized at the ensemble level, linking sequence to cellular function.
https://sites.google.com/asu.edu/zhenglab
