Exceptionally abundant exceptions: comprehensive characterization of intrinsic disorder in all domains of life

Abstract

consensus-based disorder predictions, and for the first time comprehensively characterized intrinsic disorder at proteomic and protein levels from all significant perspectives, including abundance, cellular localization, functional roles, evolution, and impact on structural coverage. We show that intrinsic disorder is more abundant and has a unique profile in eukaryotes. We map disorder into archaea, bacterial and eukaryotic cells, and demonstrate that it is preferentially located in some cellular compartments. Functional analysis that considers over 1,200 annotations shows that certain functions are exclusively implemented by intrinsically disordered proteins and regions, and that some of them are specific to certain domains of life. We reveal that disordered regions are often targets for various post-translational modifications, but primarily in the eukaryotes and viruses. Using a phylogenetic tree for 14 eukaryotic and 112 bacterial species, we analyzed relations between disorder, sequence conservation and evolutionary speed. We provide a complete analysis that clearly shows that intrinsic disorder is exceptionally and uniquely abundant in each domain of life. Keywords Intrinsic disorder · Intrinsically disordered proteins · Intrinsically disordered regions · Cellular localization · Post-translational modifications · Evolutionary speed IntroductionIt is now recognized that in addition to globular, transmembrane and fibrillar proteins that are known to be characterized by unique three dimensional (3D)-structure, there is another tribe of proteins, which, being biologically functional, do not have unique 3D-structures in their native Abstract Recent years witnessed increased interest in intrinsically disordered proteins and regions. These proteins and regions are abundant and possess unique structural features and a broad functional repertoire that complements ordered proteins. However, modern studies on the abundance and functions of intrinsically disordered proteins and regions are relatively limited in size and scope of their analysis. To fill this gap, we performed a broad and detailed computational analysis of over 6 million proteins from 59 archaea, 471 bacterial, 110 eukaryotic and 325 viral proteomes. We used arguably more accurate Electronic supplementary material The online version of this article (doi:10.1007/s00018-014-1661-9) contains supplementary material, which is available to authorized users. 3states under the physiologic conditions in vitro and in vivo [1][2][3][4][5]. The members of this novel tribe are known as intrinsically disordered proteins (IDPs). Their structures are defined as highly dynamic ensembles of flexible conformations, where sampling of a large portion of a polypeptide's available conformational space is allowed. Although IDPs and intrinsically disordered regions (IDRs) in proteins are devoid of stable 3D-structures, they possess crucial biological functions and play multiple important roles in living organisms. In fact, the conformational plasticity associated with intrins...

Paradoxes and wonders of intrinsic disorder: Stability of instability

“…[1][2][3][4][5][6][7] Several recent studies (mostly of computational nature) revealed that IDPs are very common in various proteomes, with the proteome content of IDPs being typically an indicator of both evolution and adaptation to the environment. 1,18,[42][43][44][45][46] In fact, the percentage of IDPs in proteomes is increasing from bacteria and archaebacteria, to fungi, and to eukaryotic organisms, thereby reflecting the evolutionary importance of intrinsic disorder. 42,[44][45][46] On the other hand, the role of disorder in adaptation to the environment can be illustrated by the fact that the salt, pH, and/or temperature-tolerant bacteria and Achaea typically contain more IDPs than their mesophilic and salt/pH-sensitive counterparts.…”

“…1,18,[42][43][44][45][46] In fact, the percentage of IDPs in proteomes is increasing from bacteria and archaebacteria, to fungi, and to eukaryotic organisms, thereby reflecting the evolutionary importance of intrinsic disorder. 42,[44][45][46] On the other hand, the role of disorder in adaptation to the environment can be illustrated by the fact that the salt, pH, and/or temperature-tolerant bacteria and Achaea typically contain more IDPs than their mesophilic and salt/pH-sensitive counterparts. 31,47 Many aspects related to the structure, conformational behavior and functionality of IDPs look rather strange from the viewpoint of "traditional" ordered proteins.…”

How disordered is my protein and what is its disorder for? A guide through the “dark side” of the protein universe

“…1 In fact, computational studies suggest that all proteomes of organisms in all kingdoms of life and all viral proteomes analyzed so far have considerable quantities of IDPs and IDPRs. [2][3][4][5][6][7][8] It has also been shown that the length and frequency of disordered regions are both greater in organisms of higher complexity, with at least one third of all eukaryotic proteins containing long IDPRs 4 and more than one tenth of these proteins being fully disordered. 9 Furthermore, considerably less than 30% of the crystal structures in the Protein Data Bank (PDB) are known to have no disorder.…”

The multifaceted roles of intrinsic disorder in protein complexes

“…The structure-less intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are commonly found in various proteomes [1][2][3][4][5][6], where they functionally complement ordered proteins and domains, typically playing important roles in cell signaling, as well as regulating and controlling various crucial biological processes [7][8][9][10][11][12][13][14][15][16][17][18][19]. IDPs/IDPRs are very promiscuous binders that are constantly involved in various interactions with diverse partners [20,21] and are known to play key roles in protein-protein interaction networks [13,[22][23][24][25][26].…”