The interplay between structure and function in intrinsically unstructured proteins

Abstract

Intrinsically unstructured proteins (IUPs) are common in various proteomes and occupy a unique structural and functional niche in which function is directly linked to structural disorder. The evidence that these proteins exist without a welldefined folded structure in vitro is compelling, and justifies considering them a separate class within the protein world. In this paper, novel advances in the rapidly advancing field of IUPs are reviewed, with the major attention directed to the evidence of their unfolded character in vivo, the interplay of their residual structure and their various functional modes and the functional benefits their malleable structural state provides. Via all these details, it is demonstrated that in only a couple of years after its conception, the idea of protein disorder has already come of age and transformed our basic concepts of protein structure and function.

Regulation of Escherichia coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products

“…These results are typical of intrinsically disordered proteins (IDPs), which have significantly less secondary or tertiary structure in vitro than other proteins (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). This class of proteins has been previously called natively denatured, natively unfolded, and intrinsically unstructured, among other names (21).…”

“…The CD and proteolysis results at physiological concentrations are typical of IDPs, which lack significant ␣-helix and ␤-sheet structure in vitro (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). We therefore used PONDR protein disorder-prediction programs (30) to test the similarity of UmuDЈ 2 and UmuD 2 to known disordered sequences.…”

“…IDPs often have important roles in regulation because of an ability to alter their precise structure, and therefore they function in response to changes in the cellular environment (25). Many of these proteins obtain more typical secondary structure in vivo, although some remain disordered (22,23). The actual structure of an IDP is poorly understood, although a completely random and extended structure is probably rare (19,27).…”

The K-Segment of Maize DHN1 Mediates Binding to Anionic Phospholipid Vesicles and Concomitant Structural Changes

“…Because of high hydrophilicity, high content of Gly (.20%), and the lack of a defined threedimensional structure in the pure form (Lisse et al, 1996), DHNs have been categorized as "intrinsically disordered/unstructured proteins" or "hydrophilins" (Wright and Dyson, 1999;Garay-Arroyo et al, 2000;Tompa, 2005;Kovacs et al, 2008). On the basis of compositional and biophysical properties and their link to abiotic stresses, several functions of DHNs have been proposed, including ion sequestration (Roberts et al, 1993), water retention (McCubbin et al, 1985), and stabilization of membranes or proteins (Close, 1996(Close, , 1997.…”

Honing the in silico toolkit for detecting protein disorder

“…Such transitions may also occur in situ, either resulting from a change in the environment or in response to an interaction with a specific binding partner. This latter case appears to be particularly significant biologically since it allows for extremely specific but reversible binding between protein partners (Oldfield, Cheng, Cortese, Romero et al, 2005;Tompa, 2005;Wright & Dyson, 1999). Examples of such interactions include enzyme-substrate, receptor-ligand, protein-protein, protein-RNA and protein-DNA interactions.…”