Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

Gábor Erdos; Bálint Mészáros; Dana Reichmann; Zsuzsanna Dosztányi

The key to the extraordinary versatility of proteins lies in their specific structural properties that precisely suit their individual functions. For example, enzymes typically need to adopt a welldefined conformation that ensures the correct orientation of their active site residues, as required for optimal catalytic activity. In contrast, intrinsically disordered proteins and protein regions (IDPs/IDRs) lack a well-defined structure in isolation, and are best characterized by an ensemble of rapidly interconverting conformations [1] . The specific structural properties of IDPs enable them to carry out a different set of functions, which could not be fulfilled by relatively rigid globular domains [2, 3] . As a result, the function of many IDPs directly originates from their high intrinsic flexibility, enabling them to act as linkers or spacers [3, 4] . However, there is an emerging understanding that the structural behaviour of IDPs is often context-dependent: a disorder-to-order or order-to-disorder transition can be induced as a result of binding to specific macromolecular partners, undergoing post-translational modifications, or changes in environmental factors such as pH and temperature [5] . Recently, redox conditions have emerged as another important factor that can regulate conditional disorder [6] . The growing number of examples of redox-regulated conditionally disordered proteins indicates that this is an important mechanism triggered in response to various forms of oxidative stress or to naturally occurring changes in redox potential [6, 7] .