Orderly order in protein intrinsic disorder distribution: disorder in 3500 proteomes from viruses and the three domains of life

Xue, Bin; Dunker, A. Keith; Uversky, Vladimir N.

doi:10.1080/07391102.2012.675145

Cited by 474 publications

(475 citation statements)

References 80 publications

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“…Some have hypothesized that intrinsically disordered hub proteins are advantageous in complex systems because they simplify multicomponent networks by allowing many binding partners to be organized around a single hub (15,14). Dozens of different proteins are localized specifically to Caulobacter cell poles (2).…”

Section: Discussionmentioning

confidence: 99%

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Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Holmes

Follett

Hai-bi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

144

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Despite their relative simplicity, bacteria have complex anatomy at the subcellular level. At the cell poles of Caulobacter crescentus, a 177-amino acid (aa) protein called PopZ self-assembles into 3D polymeric superstructures. Remarkably, we find that this assemblage interacts directly with at least eight different proteins, which are involved in cell cycle regulation and chromosome segregation. The binding determinants within PopZ include 24 aa at the N terminus, a 32-aa region near the C-terminal homo-oligomeric assembly domain, and portions of an intervening linker region. Together, the N-terminal 133 aa of PopZ are sufficient for interacting with all binding partners, even in the absence of homooligomeric assembly. Structural analysis of this region revealed that it is intrinsically disordered, similar to p53 and other hub proteins that organize complex signaling networks in eukaryotic cells. Through live-cell photobleaching, we find rapid binding kinetics between PopZ and its partners, suggesting many pole-localized proteins become concentrated at cell poles through rapid cycles of binding and unbinding within the PopZ scaffold. We conclude that some bacteria, similar to their eukaryotic counterparts, use intrinsically disordered hub proteins for network assembly and subcellular organization.PopZ | intrinsically disordered protein | bacteria | Caulobacter | hub protein

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Section: Discussionmentioning

confidence: 99%

“…Eukaryotic genomes, which produce many complex networks, contain a relatively high amount of protein disorder (14), and this has led to the hypothesis that the evolution of higher organisms has favored intrinsically disordered protein interactions as a means of handling complexity (15).…”

Section: Significancementioning

confidence: 99%

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Holmes

Follett

Hai-bi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

144

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“…Numerous computational studies have revealed that IDPs/ IDPRs are more common in eukaryotes than in less complex organisms (82)(83)(84)(85)(86)(87)(88)(89)(90). Furthermore, regions of eukaryotic mRNA affected by alternative splicing often code for IDPRs, suggesting that the invention of this intrinsic disorder/alternative splicing duet was an evolutionary breakthrough that eventually generated multicellular organisms (91).…”

Section: Evolution Of Intrinsic Disorder: Back To the Futurementioning

confidence: 99%

“…Recent years have witnessed a dramatic change in the understanding of the natural abundance of IDPs/IDPRs from some obscure, rare, and easily countable exceptions (in the early days), to the currently accepted abundant normality, where the prevalence of IDPs/IDPRs in various proteomes and biological processes is a well recognized reality (82)(83)(84)(85)(86)(87)(88)(89)(90). In other words, protein science transitioned from searching for "Where can you find disorder?"…”

Section: Natural Abundance Of Idps: Where Do You Not Find Disorder?mentioning

confidence: 99%

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Uversky

2016

Journal of Biological Chemistry

Self Cite

172

163

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Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs.Brief Introduction: Why Those Proteins Are Clouds and Why Those Clouds Are Dancing "Dancing protein clouds" is a joke from a time when the newly born field of protein intrinsic disorder was trying to find an appropriate term to describe biologically active proteins without unique structures. The need for a specific term was determined by the clear recognition that those structureless functional proteins were fundamentally different from the "normal" globular proteins that used information encoded in their amino acid sequences to fold into specific, aperiodic crystal-like structures needed for specific biological functions. Fig. 1 reflects these attempts by representing different terms used in literature to describe such "strange" or "abnormal" proteins and shows that the "dancing protein clouds" expression is formed by superimposing "dancing proteins" and "protein clouds" descriptors. Although the phrase "dancing protein clouds" sounds like a parody, the term actually has deep meanings. The presence of a unique structure in a given protein means that when one would look at the sample containing this protein, s/he would find that all protein molecules are alike, that the structure of an individual molecule barely changes over time, and that the ensemble-averaged (or time-averaged) structure is identical, or at least very similar, to the structures of all individual protein molecules in that sample. In other words, if one would overlay all those individual structures, a crisp and clear image would be generated, similar to those found in the Protein Data Bank (PDB), and this ensemble-averaged structure would not change much over time. On the other hand, the lack of a unique structure in a given protein would create a highly dynamic ensemble, members of which would possess very different structures at any given moment, and the structure of any given molecule would change dramatically over time (therefore the "dancing protein" analogy). If one would try to overlay all those structures,...

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“…IDPs/IDPRs do not have a unique 3D structure as a whole or in part and exist as dynamic ensembles characterized by different degree and depth of disorder. 24 IDPs are abundant in all proteomes [25][26] and possess a wide spectrum of biological functions that are typically related to regulation, signaling, and control pathways, promote the assembly of supra-molecular complexes, and complement the functions of ordered proteins. 24 IDPs/IDPRs possess complex 'anatomy' (they contain multiple, relatively short functional elements), which contributes to their unique 'physiology' (an ability to be involved in interaction with, regulation of and control by multiple structurally unrelated partners).…”

mentioning

confidence: 99%

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

et al. 2013

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It is recognized now that intrinsically disordered proteins (IDPs), which do not have unique 3D structures as a whole or in noticeable parts, constitute a significant fraction of any given proteome. IDPs are characterized by an astonishing structural and functional diversity that defines their ability to be universal regulators of various cellular pathways. Programmed cell death (PCD) is one of the most intricate cellular processes where the cell uses specialized cellular machinery and intracellular programs to kill itself. This cell-suicide mechanism enables metazoans to control cell numbers and to eliminate cells that threaten the animal's survival. PCD includes several specific modules, such as apoptosis, autophagy, and programmed necrosis (necroptosis). These modules are not only tightly regulated but also intimately interconnected and are jointly controlled via a complex set of protein-protein interactions. To understand the role of the intrinsic disorder in controlling and regulating the PCD, several large sets of PCD-related proteins across 28 species were analyzed using a wide array of modern bioinformatics tools. This study indicates that the intrinsic disorder phenomenon has to be taken into consideration to generate a complete picture of the interconnected processes, pathways, and modules that determine the essence of the PCD. We demonstrate that proteins involved in regulation and execution of PCD possess substantial amount of intrinsic disorder. We annotate functional roles of disorder across and within apoptosis, autophagy, and necroptosis processes. Disordered regions are shown to be implemented in a number of crucial functions, such as protein-protein interactions, interactions with other partners including nucleic acids and other ligands, are enriched in post-translational modification sites, and are characterized by specific evolutionary patterns. We mapped the disorder into an integrated network of PCD pathways and into the interactomes of selected proteins that are involved in the p53-mediated apoptotic signaling pathway.

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Orderly order in protein intrinsic disorder distribution: disorder in 3500 proteomes from viruses and the three domains of life

Cited by 474 publications

References 80 publications

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

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