Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins
- PMID: 16444738
- DOI: 10.1002/prot.20888
Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins
Abstract
Proteins named 14-3-3 can bind more than 200 different proteins, mostly (but not exclusively) when they are at a phosphorylated state. These partner proteins are involved in different cellular processes, such as cell signaling, transcription factors, cellular morphology, and metabolism; this suggests pleiotropic functionality for 14-3-3 proteins. Recent efforts to establish a rational classification of 14-3-3 binding partners showed neither structural nor functional relatedness in this group of proteins. Using three natural predictors of disorder in proteins, and the structural available information, we show that >90% of 14-3-3 protein partners contain disordered regions. This percentage is significantly high when compared with recent studies on cell signaling and cancer-related proteins or RNA chaperons. More important, almost all 14-3-3-binding sites are inside disordered regions, this reinforcing the importance of structural disorder in this class of proteins. We also propose that a disorder-to-order transition occurs in the binding of 14-3-3 proteins with their partners. We discuss the consequences of the latter for consensus binding sequences, specificity, affinity, and thermodynamic control.
2006 Wiley-Liss, Inc.
Similar articles
-
Protein conformational transitions coupled to binding in molecular recognition of unstructured proteins: deciphering the effect of intermolecular interactions on computational structure prediction of the p27Kip1 protein bound to the cyclin A-cyclin-dependent kinase 2 complex.Proteins. 2005 Feb 15;58(3):706-16. doi: 10.1002/prot.20351. Proteins. 2005. PMID: 15609350
-
Analysis of molecular recognition features (MoRFs).J Mol Biol. 2006 Oct 6;362(5):1043-59. doi: 10.1016/j.jmb.2006.07.087. Epub 2006 Aug 4. J Mol Biol. 2006. PMID: 16935303
-
Entropy capacity determines protein folding.Proteins. 2006 Apr 1;63(1):144-54. doi: 10.1002/prot.20851. Proteins. 2006. PMID: 16400647
-
Role of intrinsically disordered protein regions/domains in transcriptional regulation.Life Sci. 2009 Feb 13;84(7-8):189-93. doi: 10.1016/j.lfs.2008.12.002. Epub 2008 Dec 24. Life Sci. 2009. PMID: 19109982 Review.
-
Limitations of induced folding in molecular recognition by intrinsically disordered proteins.Chemphyschem. 2009 Jul 13;10(9-10):1415-9. doi: 10.1002/cphc.200900205. Chemphyschem. 2009. PMID: 19462392 Review.
Cited by
-
Analysis of 14-3-3 isoforms expressed in photoreceptors.Exp Eye Res. 2018 May;170:108-116. doi: 10.1016/j.exer.2018.02.022. Epub 2018 Feb 24. Exp Eye Res. 2018. PMID: 29486162 Free PMC article.
-
The intrinsically disordered regions of the Drosophila melanogaster Hox protein ultrabithorax select interacting proteins based on partner topology.PLoS One. 2014 Oct 6;9(10):e108217. doi: 10.1371/journal.pone.0108217. eCollection 2014. PLoS One. 2014. PMID: 25286318 Free PMC article.
-
Analysis of the native conformation of the LIR/AIM motif in the Atg8/LC3/GABARAP-binding proteins.Autophagy. 2015;11(12):2153-9. doi: 10.1080/15548627.2015.1111503. Autophagy. 2015. PMID: 26565669 Free PMC article.
-
Conformational changes in the negative arm of the circadian clock correlate with dynamic interactomes involved in post-transcriptional regulation.Cell Rep. 2023 Apr 25;42(4):112376. doi: 10.1016/j.celrep.2023.112376. Epub 2023 Apr 10. Cell Rep. 2023. PMID: 37043358 Free PMC article.
-
14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases.Trends Pharmacol Sci. 2021 Apr;42(4):226-238. doi: 10.1016/j.tips.2021.01.001. Epub 2021 Jan 28. Trends Pharmacol Sci. 2021. PMID: 33518287 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
