Intrinsic protein disorder and dynamics in regulation and signaling

The traditional view of protein structure-function relationships posits that a well-defined three-dimensional (3D) structure is required for function. However, it is now well appreciated that many biological functions are performed by highly dynamic proteins or protein domains that, in isolation, lack secondary and/or tertiary structure under physiological conditions. These are termed intrinsically disordered (or unstructured) proteins (termed IDPs). IDPs exist in organisms from all kingdoms of life and are most prevalent in eukaryotes. IDPs exhibit distinct, functionally relevant features when compared to globular proteins. For example, IDPs frequently fold upon binding to their biological targets. Further, IDPs often interact with numerous targets, a phenomenon termed "binding diversity". Interestingly, however, some IDPs perform their biological function(s) while remaining highly disordered (e.g., some components of the NPC). IDPs often remain dynamic when bound to their functional partners, enabling signal transduction via post-translational modifications. We will survey the general features of IDPs and also discuss several examples illustrating how their dynamic features mediate binding diversity and signal transduction involved in regulation of cell division and apoptosis.