oa Editorial [Hot Topic: Intrinsically Disordered Proteins: A Focused Look at Fuzzy Subjects (Guest Editor: Vladimir N. Uversky)]

INTRODUCTION Recent bioinformatics studies revealed that proteins without stable tertiary and/or secondary structure are very common in nature [1-6]. These highly fluctuable proteins are biologically active yet fail to form specific 3D structures, existing as collapsed or extended dynamic conformational ensembles [3, 7-13]. They constitute an important addition to the protein kingdom [14], which for a long time was considered to contain globular, transmembrane, and fibrous proteins. These non-rigid, but biologically important proteins and regions are known by different names, such as pliable [15], floppy [16], rheomorphic [17], flexible [18], mobile [19], partially folded [20], natively denatured [21], natively unfolded [3, 22], natively disordered [11], intrinsically unstructured [8, 10], intrinsically denatured, [21] intrinsically unfolded [22], intrinsically disordered [9], vulnerable [23], chameleon [24], malleable [25], 4D [26], dancing proteins [27], protein clouds [12, 28], 32 proteins [24], etc. Among all these terms, the expression “intrinsically disordered protein (IDP)” is used most frequently in recent literature, and by a silent agreement is considered as the most appropriate descriptor of the phenomenon. The number of structurally and functionally characterized IDPs and proteins with disordered regions and domains is rapidly amplifying, illustrating the growing interest to this class of proteins. There are several reasons for this growing attention to IDPs. Some of them are outlined below. The first reason is the structure-function relationship. The existence of biologically active but extremely flexible proteins questions the assumption that rigid well-folded 3Dstructure is required for protein function [8-10, 12, 29]. In fact, IDPs were shown to carry out a number of crucial biological functions that are complementary to the functional repertoire of structured (ordered) proteins [9, 30-35]. Evolutionary persistence of these proteins represents strong evidence in favor of their importance and raises intriguing questions on the role of protein disorder in biological processes [7, 36]. In any given organism, IDPs constitute a unique unfoldome; i.e., a functionally broad and densely populated subset of the proteome [37-38]. IDPs are common across the three domains of life, being especially abundant in the eukaryotic proteomes [2, 6]. Signaling sequences are commonly located within regions of intrinsic disorder [5, 9, 30]. Disorder-to-order transitions in an IDP are coupled with the possibility for a single protein/region to adopt different structures in complexes with different partners [39-40]. The disorder- based signaling is modulated by various posttranslational modifications and alternative splicing [5, 41].....