Effects of macromolecular crowding on the intrinsically disordered proteins c-Fos and p27(Kip1)
- PMID: 11749217
- DOI: 10.1021/bm015502z
Effects of macromolecular crowding on the intrinsically disordered proteins c-Fos and p27(Kip1)
Abstract
A number of biologically active proteins exhibit intrinsic structural disorder in vitro under thermodynamically ideal conditions. In vivo, however, proteins exist in a crowded, thermodynamically nonideal environment. We tested the hypothesis that intrinsically disordered proteins adopt stable structure under crowded conditions in which excluded volume is predicted to stabilize compact, native conformations. In the presence of macromolecular crowding agents, neither the intrinsically disordered C-terminal activation domain of c-Fos nor the kinase-inhibition domain of p27(Kip1) undergoes any significant conformational change that is detected by changes in either circular dichroism or fluorescence spectra. We conclude that molecular crowding effects are not necessarily sufficient to induce ordered structure in intrinsically disordered proteins.
Similar articles
-
Functional consequences of preorganized helical structure in the intrinsically disordered cell-cycle inhibitor p27(Kip1).Biochemistry. 2002 Jan 22;41(3):752-9. doi: 10.1021/bi015763t. Biochemistry. 2002. PMID: 11790096
-
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
-
Protein conformational transitions coupled to binding in molecular recognition of unstructured proteins: hierarchy of structural loss from all-atom Monte Carlo simulations of p27Kip1 unfolding-unbinding and structural determinants of the binding mechanism.Biopolymers. 2004 Dec 5;75(5):420-33. doi: 10.1002/bip.20149. Biopolymers. 2004. PMID: 15468065
-
Intrinsically disordered proteins in crowded milieu: when chaos prevails within the cellular gumbo.Cell Mol Life Sci. 2018 Nov;75(21):3907-3929. doi: 10.1007/s00018-018-2894-9. Epub 2018 Jul 31. Cell Mol Life Sci. 2018. PMID: 30066087 Free PMC article. Review.
-
p27 Expression, a cyclin dependent kinase inhibitor in breast carcinoma.Adv Clin Path. 1999 Oct;3(4):119-27. Adv Clin Path. 1999. PMID: 10936889 Review.
Cited by
-
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.
-
Folding propensity of intrinsically disordered proteins by osmotic stress.Mol Biosyst. 2016 Nov 15;12(12):3695-3701. doi: 10.1039/c6mb00512h. Mol Biosyst. 2016. PMID: 27752679 Free PMC article.
-
Protein flexibility, not disorder, is intrinsic to molecular recognition.F1000 Biol Rep. 2013;5:2. doi: 10.3410/B5-2. Epub 2013 Jan 11. F1000 Biol Rep. 2013. PMID: 23361309 Free PMC article.
-
Identification, analysis, and prediction of protein ubiquitination sites.Proteins. 2010 Feb 1;78(2):365-80. doi: 10.1002/prot.22555. Proteins. 2010. PMID: 19722269 Free PMC article.
-
FlgM gains structure in living cells.Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12681-4. doi: 10.1073/pnas.202331299. Epub 2002 Sep 23. Proc Natl Acad Sci U S A. 2002. PMID: 12271132 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous
