Abstract
The classical and idealistic consideration of the protein universe as a set of well-ordered proteinaceous machines with unique spatial organizations conducting unique biological functions is changed because of the recognition that proteins can fold, misfold, or be disordered to different degree. Functional repertoires of intrinsically disordered proteins complement functions of ordered proteins, whereas protein misfolding and concomitant oligomerization, aggregation, and fibrillation are related to the pathogenesis of numerous human diseases. Flexible proteins can undergo liquid–liquid phase separation, which is at the heart of the biogenesis of numerous membrane-less organelles. Many of these aspects were highlighted in four talks delivered at the SP16 Session at the 20th IUPAB congress, 45th Annual Meeting of SBBf, and 50th Annual Meeting of SBBq.
This is a preview of subscription content, log in via an institution to check access.
References
Akbayrak IY, Caglayan SI, Ozcan Z, Uversky VN, Coskuner-Weber O (2020) Current challenges and limitations in the studies of intrinsically disordered proteins in neurodegenerative diseases by computer simulations. Curr Alzheimer Res 17(9):805–818. https://doi.org/10.2174/1567205017666201109094908
Brangwynne CP, Eckmann CR, Courson DS, Rybarska A, Hoege C, Gharakhani J, Julicher F, Hyman AA (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324(5935):1729–1732. https://doi.org/10.1126/science.1172046
Coskuner-Weber O, Uversky VN (2018) Insights into the molecular mechanisms of Alzheimer's and Parkinson's diseases with molecular simulations: understanding the roles of artificial and pathological missense mutations in intrinsically disordered proteins related to pathology. Int J Mol Sci 19 (2). doi:https://doi.org/10.3390/ijms19020336
Dobson CM (2003) Protein folding and misfolding. Nature 426(6968):884–890. https://doi.org/10.1038/nature02261
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. J Mol Graph Model 19(1):26–59. https://doi.org/10.1016/s1093-3263(00)00138-8
Fatafta H, Samantray S, Sayyed-Ahmad A, Coskuner-Weber O, Strodel B (2021) Molecular simulations of IDPs: from ensemble generation to IDP interactions leading to disorder-to-order transitions. Prog Mol Biol Transl Sci 183:135–185. https://doi.org/10.1016/bs.pmbts.2021.06.003
Fonin AV, Silonov SA, Shpironok OG, Antifeeva IA, Petukhov AV, Romanovich AE, Kuznetsova IM, Uversky VN, Turoverov KK (2021) The role of non-specific interactions in canonical and ALT-associated PML-bodies formation and dynamics. Int J Mol Sci 22 (11). doi:https://doi.org/10.3390/ijms22115821
Hyman AA, Weber CA, Julicher F (2014) Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol 30:39–58. https://doi.org/10.1146/annurev-cellbio-100913-013325
Kulkarni P (2020) Intrinsically disordered proteins: insights from Poincare, Waddington, and Lamarck. Biomolecules 10 (11). doi:https://doi.org/10.3390/biom10111490
Kulkarni P, Getzenberg RH (2016) Disorder, promiscuous interactions, and stochasticity regulate state switching in the unstable prostate. J Cell Biochem 117(10):2235–2240. https://doi.org/10.1002/jcb.25578
Kulkarni V, Kulkarni P (2019) Intrinsically disordered proteins and phenotypic switching: implications in cancer. Prog Mol Biol Transl Sci 166:63–84. https://doi.org/10.1016/bs.pmbts.2019.03.013
Lin X, Kulkarni P, Bocci F, Schafer NP, Roy S, Tsai MY, He Y, Chen Y, Rajagopalan K, Mooney SM, Zeng Y, Weninger K, Grishaev A, Onuchic JN, Levine H, Wolynes PG, Salgia R, Rangarajan G, Uversky V, Orban J, Jolly MK (2019) Structural and dynamical order of a disordered protein: molecular insights into conformational switching of PAGE4 at the systems level. Biomolecules 9 (2). doi:https://doi.org/10.3390/biom9020077
Lopez N, Camporeale G, Salgueiro M, Borkosky SS, Visentin A, Peralta-Martinez R, Loureiro ME, de Prat-Gay G (2021) Deconstructing virus condensation. PLoS Pathog 17(10):e1009926. https://doi.org/10.1371/journal.ppat.1009926
Mooney SM, Jolly MK, Levine H, Kulkarni P (2016) Phenotypic plasticity in prostate cancer: role of intrinsically disordered proteins. Asian J Androl 18(5):704–710. https://doi.org/10.4103/1008-682X.183570
Nesterov SV, Ilyinsky NS (1868) Uversky VN (2021) Liquid-liquid phase separation as a common organizing principle of intracellular space and biomembranes providing dynamic adaptive responses. Biochim Biophys Acta Mol Cell Res 11:119102. https://doi.org/10.1016/j.bbamcr.2021.119102
Rangarajan N, Fox Z, Singh A, Kulkarni P, Rangarajan G (2015) Disorder, oscillatory dynamics and state switching: the role of c-Myc. J Theor Biol 386:105–114. https://doi.org/10.1016/j.jtbi.2015.09.013
Tompa P (2002) Intrinsically unstructured proteins. Trends Biochem Sci 27(10):527–533. https://doi.org/10.1016/s0968-0004(02)02169-2
Uversky VN (2003) Protein folding revisited. A polypeptide chain at the folding-misfolding-nonfolding cross-roads: which way to go? Cell Mol Life Sci 60 (9):1852–1871. doi:https://doi.org/10.1007/s00018-003-3096-6
Uversky VN (2016a) Dancing protein clouds: the strange biology and chaotic physics of intrinsically disordered proteins. J Biol Chem 291(13):6681–6688. https://doi.org/10.1074/jbc.R115.685859
Uversky VN (2016b) p53 Proteoforms and intrinsic disorder: an illustration of the protein structure-function continuum concept. Int J Mol Sci 17 (11). doi:https://doi.org/10.3390/ijms17111874
Uversky VN (2019) Protein intrinsic disorder and structure-function continuum. Prog Mol Biol Transl Sci 166:1–17. https://doi.org/10.1016/bs.pmbts.2019.05.003
Uversky VN, Gillespie JR, Fink AL (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41(3):415–427. https://doi.org/10.1002/1097-0134(20001115)41:3%3c415::aid-prot130%3e3.0.co;2-7
Wright PE, Dyson HJ (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 293(2):321–331. https://doi.org/10.1006/jmbi.1999.3110
Funding
Not applicable
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares no competing interests.
Ethical approval
Not applicable
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Uversky, V.N. Protein folding, misfolding, and un/non-folding: overview of the SP16 Session at the 20th IUPAB congress, 45th Annual Meeting of SBBf, and 50th Annual Meeting of SBBq. Biophys Rev 13, 879–882 (2021). https://doi.org/10.1007/s12551-021-00885-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12551-021-00885-8