Intrinsically Disordered Proteins

Abstract

Many biologically active proteins fail to form unique three-dimensional (3D) structures under physiological conditions, either along their entire lengths or locally. These proteins are known as intrinsically disordered proteins (IDPs) among several other names. The discovery of these proteins challenged the traditional protein structure paradigm, according to which a unique well-defined structure was required for the correct function of a protein and therefore a unique structure defines a unique function of a protein. IDPs are structurally and functionally very different from ordered proteins, and therefore require special experimental and computational tools for identification and analyses. They are highly abundant in nature; and, in any given organism, they constitute a functionally broad and densely populated unfoldome. They possess a number of crucial biological functions that complement the functional repertoire of structured (ordered) proteins. They are very important players in cell signaling, protein–protein interaction networks and gene regulation networks. Their signaling activities are modulated by numerous posttranslational modifications and, in multicellular eukaryotes, by alternative splicing. Some IDPs in some cases can fold into a specific 3D structure after binding to natural partners. These proteins are tightly controlled inside the cell and their dysregulation and misbehavior is frequently associated with the development of various pathological conditions.