Distinct conformational states of nuclear receptor-bound CRSP-Med complexes
- PMID: 15195149
- DOI: 10.1038/nsmb789
Distinct conformational states of nuclear receptor-bound CRSP-Med complexes
Abstract
The human CRSP-Med coactivator complex is targeted by a diverse array of sequence-specific regulatory proteins. Using EM and single-particle reconstruction techniques, we recently completed a structural analysis of CRSP-Med bound to VP16 and SREBP-1a. Notably, these activators induced distinct conformational states upon binding the coactivator. Ostensibly, these different conformational states result from VP16 and SREBP-1a targeting distinct subunits in the CRSP-Med complex. To test this, we conducted a structural analysis of CRSP-Med bound to either thyroid hormone receptor (TR) or vitamin D receptor (VDR), both of which interact with the same subunit (Med220) of CRSP-Med. Structural comparison of TR- and VDR-bound complexes (at a resolution of 29 A) indeed reveals a shared conformational feature that is distinct from other known CRSP- Med structures. Importantly, this nuclear receptor-induced structural shift seems largely dependent on the movement of Med220 within the complex.
Similar articles
-
Structure, function, and activator-induced conformations of the CRSP coactivator.Science. 2002 Feb 8;295(5557):1058-62. doi: 10.1126/science.1065249. Science. 2002. PMID: 11834832
-
Structure and function of CRSP/Med2; a promoter-selective transcriptional coactivator complex.Mol Cell. 2004 Jun 4;14(5):675-83. doi: 10.1016/j.molcel.2004.05.014. Mol Cell. 2004. PMID: 15175162
-
Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation.Genes Dev. 2002 Jun 1;16(11):1339-44. doi: 10.1101/gad.987602. Genes Dev. 2002. PMID: 12050112 Free PMC article.
-
Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex.Nature. 1999 Apr 29;398(6730):824-8. doi: 10.1038/19783. Nature. 1999. PMID: 10235266
-
Vitamin D analogs and coactivators.Anticancer Res. 2006 Jul-Aug;26(4A):2717-21. Anticancer Res. 2006. PMID: 16886682 Review.
Cited by
-
Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues.Genes Dev. 2021 May 1;35(9-10):729-748. doi: 10.1101/gad.346791.120. Epub 2021 Apr 22. Genes Dev. 2021. PMID: 33888560 Free PMC article.
-
Trichoderma reesei XYR1 activates cellulase gene expression via interaction with the Mediator subunit TrGAL11 to recruit RNA polymerase II.PLoS Genet. 2020 Sep 2;16(9):e1008979. doi: 10.1371/journal.pgen.1008979. eCollection 2020 Sep. PLoS Genet. 2020. PMID: 32877410 Free PMC article.
-
Twenty years of Mediator complex structural studies.Biochem Soc Trans. 2019 Feb 28;47(1):399-410. doi: 10.1042/BST20180608. Epub 2019 Feb 7. Biochem Soc Trans. 2019. PMID: 30733343 Free PMC article. Review.
-
Mediator Complex Subunits MED2, MED5, MED16, and MED23 Genetically Interact in the Regulation of Phenylpropanoid Biosynthesis.Plant Cell. 2017 Dec;29(12):3269-3285. doi: 10.1105/tpc.17.00282. Epub 2017 Dec 4. Plant Cell. 2017. PMID: 29203634 Free PMC article.
-
The complex structure and function of Mediator.J Biol Chem. 2018 Sep 7;293(36):13778-13785. doi: 10.1074/jbc.R117.794438. Epub 2017 Sep 14. J Biol Chem. 2018. PMID: 28912271 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources