Introducing Unfoldome and Unfoldomics

Recent studies revealed that functional proteins without unique 3-D structures are highly abundant in nature. These intrinsically disordered proteins (IDPs) possess a number of crucial biological functions that are complementary to functions of structured (ordered) proteins. In any given organism, IDPs constitute a functionally broad and densely populated unfoldome; i.e., a set of unstructured proteins in a proteome. Being structurally and functionally very different from ordered proteins, IDPs require special experimental and computational tools for their identification and analyses. These specific investigative approaches underlie unfoldomics.

IDPs are common across the three domains of life, being especially abundant in the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are located within regions of intrinsic disorder. Disorder-to-order transitions in an IDP are coupled with the adoption of different structures in complexes with different partners. The intrinsic flexibility of IDPs helps different disordered regions to bind to a common binding site on a common partner. This binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which splicing events map to regions of disorder much more often than to regions of structure. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several small molecules-potential drugs have been shown to act by blocking protein-protein interactions involving intrinsic disorder of one of the partners.

Intrinsically Disordered Proteins GRC provides a forum for the discussion of IDPs, with topics including but not limited to experimental and theoretical studies of their intrinsically flexible state, mechanisms of their interactions, their functional roles in biological systems, and their potential involvement into the pathogenesis of conformational and other diseases. This GRC will unite participants from all scientific disciplines with an interest in broadening our understanding of IDPs, ranging from biophysical studies of individual proteins to genomic and proteomic studies in whole organisms, to biomedical investigations on the molecular mechanisms of many human diseases.