The functional benefits of protein disorder

Intrinsically unstructured proteins, which exist and function without a well-defined folded structure, constitute a newly recognized class of the protein world. Such proteins are common in living organisms and occupy a unique niche in which function is intimately linked with structural disorder. In this paper it is shown that these proteins assume no compact structural state in vivo, despite a significant macromolecular crowding effect that could force them fold under cellular conditions. Further, it is argued that they are not fully unstructured, but contain functionally indispensable residual structure. Their recently suggested functional classification is delineated and extended through novel examples. Finally, the functional benefits of structural disorder encompassing some newly recognized features, such as direct proteasomal degradation and chaperone activity, will be thoroughly discussed. Through all these details, the message is conveyed that our understanding of protein function will not be complete as long as the functional benefits of protein disorder are not fully appreciated. (C) 2003 Elsevier B.V. All rights reserved.