Intrinsically disordered proteins

Conformational flexibility in SUMO-1 protein (PDB:1a5r). The central part shows relatively ordered structure. Conversely, the N- and C-terminal regions (left and right, respectively) show ‘intrinsic disorder’, although a short helical region persists in the N-terminal tail. Ten alternative NMR models were morphed. Secondary structure elements: α-helices (red), β-strands (blue arrows). [1]

In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure,[2][3][4] typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs range from fully unstructured to partially structured and include random coil, molten globule-like aggregates, or flexible linkers in large multi-domain proteins. They are sometimes considered as a separate class of proteins along with globular, fibrous and membrane proteins.[5]

IDPs are a very large and functionally important class of proteins and their discovery has disproved the idea that three-dimensional structures of proteins must be fixed to accomplish their biological functions. For example, IDPs have been identified to participate in weak multivalent interactions that are highly cooperative and dynamic, lending them importance in DNA regulation and in cell signaling.[6][7] Many IDPs can also adopt a fixed three-dimensional structure after binding to other macromolecules. Overall, IDPs are different from structured proteins in many ways and tend to have distinctive function, structure, sequence, interactions, evolution and regulation.[8]

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  2. ^ Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z (2001). "Intrinsically disordered protein". Journal of Molecular Graphics & Modelling. 19 (1): 26–59. CiteSeerX 10.1.1.113.556. doi:10.1016/s1093-3263(00)00138-8. PMID 11381529.
  3. ^ Dyson HJ, Wright PE (March 2005). "Intrinsically unstructured proteins and their functions". Nature Reviews Molecular Cell Biology. 6 (3): 197–208. doi:10.1038/nrm1589. PMID 15738986. S2CID 18068406.
  4. ^ Dunker AK, Silman I, Uversky VN, Sussman JL (December 2008). "Function and structure of inherently disordered proteins". Current Opinion in Structural Biology. 18 (6): 756–64. doi:10.1016/j.sbi.2008.10.002. PMID 18952168.
  5. ^ Andreeva A, Howorth D, Chothia C, Kulesha E, Murzin AG (January 2014). "SCOP2 prototype: a new approach to protein structure mining". Nucleic Acids Research. 42 (Database issue): D310–4. doi:10.1093/nar/gkt1242. PMC 3964979. PMID 24293656.
  6. ^ Mir M, Stadler MR, Ortiz SA, Hannon CE, Harrison MM, Darzacq X, Eisen MB (December 2018). Singer RH, Struhl K, Crocker J (eds.). "Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos". eLife. 7: e40497. doi:10.7554/eLife.40497. PMC 6307861. PMID 30589412.
  7. ^ Wright PE, Dyson HJ (January 2015). "Intrinsically disordered proteins in cellular signalling and regulation". Nature Reviews. Molecular Cell Biology. 16 (1): 18–29. doi:10.1038/nrm3920. PMC 4405151. PMID 25531225.
  8. ^ van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, et al. (July 2014). "Classification of intrinsically disordered regions and proteins". Chemical Reviews. 114 (13): 6589–6631. doi:10.1021/cr400525m. PMC 4095912. PMID 24773235.