Intrinsically Disordered Proteins in Cellular Signaling and Regulation

By Peter E. Wright, H. J. Dyson. 2014

2,130 citations recorded by the source corpus.

Intrinsically disordered proteins (IDPs) are important components of the cellular signalling machinery, allowing the same polypeptide to undertake different interactions with different consequences. IDPs are subject to combinatorial post-translational modifications and alternative splicing, adding complexity to regulatory networks and providing a mechanism for tissue-specific signalling. These proteins participate in the assembly of signalling complexes and in the dynamic self-assembly of membrane-less nuclear and cytoplasmic organelles. Experimental, computational and bioinformatic analyses combine to identify and characterize disordered regions of proteins, leading to a greater appreciation of their widespread roles in biological processes.

Subfields: Molecular Biology

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Citations in the corpus

InterPro in 2017—beyond protein family and domain annotations (2016, background): “Intrinsically disordered (ID) protein regions, which do not adopt a single well-defined conformation in isolation, rely on a highly flexible state or structural plasticity to carry out their functions (40,41).”
MFIB: a repository of protein complexes with mutual folding induced by binding (2017, background): “Intrinsically disordered proteins (IDPs) do not have a stable structure under native conditions (Wright and Dyson, 1999), yet they perform crucial biological roles being deeply embedded in regulatory and signaling pathways, amongst others (Dyson and Wright, 2005; Wright and Dyson, 2015).”
Structured states of disordered proteins from genomic sequences (2016, positive): “…gene regulation, signaling, and molecular transport, spurring growing interest in so-called disordered and low-complexity sequences (Bah et al., 2015; Ferreon et al., 2013; Motlagh et al., 2014; Tokuriki and Tawfik, 2009; Uversky and Dunker, 2010; Wells et al., 2008; Wright and Dyson, 2015).”
Principles of protein structural ensemble determination. (2017, background): “It has been suggested that these proteins make up about one-third of the human proteome [10,12] and that their dynamic nature facilitates multiple interactions, making them particularly important in regulation and signalling processes [10,13].”
Transcription factors activate genes through the phase separation capacity of their activation domains (2018, background): “Many of these features have been described for IDRs that are capable of forming phase-separated condensates (Babu, 2016; Darling et al., 2018; Das et al., 2015; Dunker et al., 2015; Habchi et al., 2014; van der Lee et al., 2014; Oldfield and Dunker, 2014; Uversky, 2017; Wright and Dyson, 2015).”
ProViz—a web-based visualization tool to investigate the functional and evolutionary features of protein sequences (2016, background): “Key aspects of the visualization are numbered: (1) Protein name and species; (2) options sidebar; (3) data information sidebar; (4) data select, hide and help buttons; (5) information hover tooltip; (6) options toolbar; (7) protein architecture overview; (8) protein sequence data; (9) protein featur”
DIBS: a repository of disordered binding sites mediating interactions with ordered proteins (2017, background): “Intrinsically Disordered Proteins (IDPs) play crucial roles in biological systems most notably in regulatory and signaling networks (Wright and Dyson, 2015).”
Intrinsic protein disorder and conditional folding in AlphaFoldDB (2022, methodology): “12 Indeed, both AlphaFold-pLDDT and AlphaFold-RSA do not perform well on this task (see Figure 2c, Tables S5 and S6).”
Distinct stages in stress granule assembly and disassembly (2016, neutral): “DOI: 10.7554/eLife.18413.001”
Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule (2015, background): “Interactions mediated by MoRFs are important and play key roles in regulatory processes and in signal transduction [3], as their structural flexibility grants MoRFs the ability to mold into a precise fit for a given binding surface and, thereby, achieve high interaction specificity, which is often…”
Biphasic Control of Microtubule Severing by Tubulin Glutamylation (2016, neutral): “Posttranslational modifications of IDRs are ubiquitously used to assemble complex signaling platforms (Wright and Dyson, 2015).”
CIDER: Resources to Analyze Sequence-Ensemble Relationships of Intrinsically Disordered Proteins (2017, background): “They are associated with a variety of functions, including transcriptional regulation, cell signaling (2), chaperone activity (3), regulation of bacterial homeostasis and lifecycles, viral infectivity, and subcellular organization in eukaryotic cells (4).”
Tau protein liquid–liquid phase separation can initiate tau aggregation (2018, neutral): “Proteins that contain intrinsically disordered regions often have multiple biological functions (Wright & Dyson, 2014), and some of them aggregate in protein aggregation diseases, such as huntingtin protein in Huntington’s disease, a -synuclein in Parkinson’s disease, TDP43 and FUS in ALS, and tau…”