Predicting Binding Regions within Disordered Proteins
- PMID: 11072341
Predicting Binding Regions within Disordered Proteins
Abstract
Disordered regions are sequences within proteins that fail to fold into a fixed tertiary structure and have been shown to be involved in a variety of biological functions. We recently applied neural network predictors of disorder developed from X-ray data to several protein sequences characterized as disordered by NMR (Garner, Cannon, Romero, Obradovic and Dunker, Genome Informatics, 9:201-213, 1998). A few predictions on the NMR-characterized disordered regions were noted to contain false negative indications of order that correlated with regions of function. These and additional examples are examined in more detail here. Overall, 8 of 9 functional segments in 5 disordered proteins were identified or partially identified by this approach. The functions of these regions appear to involve binding to DNA, RNA, and proteins. These regions are known to undergo disorder-to-order transitions upon binding. This apparent ability of the predictors to identify functional regions in disordered proteins could be due to the existence of different flavors, or sub-classes of disorder, originating from the sequence of the disordered regions and perhaps owing to local inclinations toward order. These different flavors may be a characteristic that could be used to identify binding regions within proteins that are difficult to characterize structurally.
Similar articles
-
The unfoldomics decade: an update on intrinsically disordered proteins.BMC Genomics. 2008 Sep 16;9 Suppl 2(Suppl 2):S1. doi: 10.1186/1471-2164-9-S2-S1. BMC Genomics. 2008. PMID: 18831774 Free PMC article.
-
Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins.J Proteome Res. 2007 May;6(5):1917-32. doi: 10.1021/pr060394e. Epub 2007 Mar 29. J Proteome Res. 2007. PMID: 17391016 Free PMC article.
-
Evolutionary rate heterogeneity in proteins with long disordered regions.J Mol Evol. 2002 Jul;55(1):104-10. doi: 10.1007/s00239-001-2309-6. J Mol Evol. 2002. PMID: 12165847
-
Bioinformatical approaches to characterize intrinsically disordered/unstructured proteins.Brief Bioinform. 2010 Mar;11(2):225-43. doi: 10.1093/bib/bbp061. Epub 2009 Dec 10. Brief Bioinform. 2010. PMID: 20007729 Review.
-
Multitude of binding modes attainable by intrinsically disordered proteins: a portrait gallery of disorder-based complexes.Chem Soc Rev. 2011 Mar;40(3):1623-34. doi: 10.1039/c0cs00057d. Epub 2010 Nov 3. Chem Soc Rev. 2011. PMID: 21049125 Review.
Cited by
-
Targeting intrinsically disordered proteins in neurodegenerative and protein dysfunction diseases: another illustration of the D(2) concept.Expert Rev Proteomics. 2010 Aug;7(4):543-64. doi: 10.1586/epr.10.36. Expert Rev Proteomics. 2010. PMID: 20653509 Free PMC article. Review.
-
Unveiling the Metal-Dependent Aggregation Properties of the C-terminal Region of Amyloidogenic Intrinsically Disordered Protein Isoforms DPF3b and DPF3a.Int J Mol Sci. 2022 Dec 4;23(23):15291. doi: 10.3390/ijms232315291. Int J Mol Sci. 2022. PMID: 36499617 Free PMC article.
-
The unfoldomics decade: an update on intrinsically disordered proteins.BMC Genomics. 2008 Sep 16;9 Suppl 2(Suppl 2):S1. doi: 10.1186/1471-2164-9-S2-S1. BMC Genomics. 2008. PMID: 18831774 Free PMC article.
-
Short Linear Motifs recognized by SH2, SH3 and Ser/Thr Kinase domains are conserved in disordered protein regions.BMC Genomics. 2008 Sep 16;9 Suppl 2(Suppl 2):S26. doi: 10.1186/1471-2164-9-S2-S26. BMC Genomics. 2008. PMID: 18831792 Free PMC article.
-
Intrinsically disordered proteins in the nucleus of human cells.Biochem Biophys Rep. 2015 Mar 24;1:33-51. doi: 10.1016/j.bbrep.2015.03.003. eCollection 2015 May. Biochem Biophys Rep. 2015. PMID: 29124132 Free PMC article.