Intrinsically disordered proteins in cellular signalling and regulation

• Published in: Nature reviews. Molecular cell biology Vol. 16; no. 1; pp. 18 - 29
• Main Authors: Wright, Peter E., Dyson, H. Jane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2015; Nature Publishing Group
• Subjects: 631/337/470; 631/57/2269; 631/80/470/460; 631/80/86; Alternative Splicing - physiology; Animals; Biochemistry; Cancer Research; Cell Biology; Developmental Biology; Humans; Intrinsically Disordered Proteins - genetics; Intrinsically Disordered Proteins - metabolism; Life Sciences; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Organ Specificity - physiology; Protein Processing, Post-Translational - physiology; Proteins; review-article; Signal Transduction - physiology; Stem Cells
• ISSN: 1471-0072; 1471-0080; 1471-0080
• DOI: 10.1038/nrm3920

Key Points Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins that may also contain structured domains mediate crucial signalling processes in eukaryotic cells. Disorder is advantageous in cell signalling because disordered sequences have the potential to bind to multiple partners, often using different structures. Disordered regions are relatively accessible, often contain multiple binding motifs and are frequently the sites for post-translational modification, an important mediator of the control of signalling pathways. Disordered proteins have central roles in the formation of higher-order signalling assemblies and in the operation of circadian clocks. Intrinsically disordered proteins (IDPs) are key components of the cellular signalling machinery. Their flexible conformation enables them to interact with different partners and to participate in the assembly of signalling complexes and membrane-less organelles; this leads to different cellular outcomes. Post-translational modification of IDPs and alternative splicing add complexity to regulatory networks. 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.