6h02

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Crystal structure of human Mediator subunit MED23Crystal structure of human Mediator subunit MED23

Structural highlights

6h02 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MED23_HUMAN] Autosomal recessive non-syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.

Function

[MED23_HUMAN] Required for transcriptional activation subsequent to the assembly of the pre-initiation complex (By similarity). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Required for transcriptional activation by adenovirus E1A protein. Required for ELK1-dependent transcriptional activation in response to activated Ras signaling.[1] [2] [3]

Publication Abstract from PubMed

Sur2 is a metazoan Mediator subunit that interacts with the adenovirus E1A protein and functions in a mitogen-activated protein kinase pathway required for vulva development in Caenorhabditis elegans. We generated sur2-/- embryonic stem cells to analyze its function as a mammalian Mediator component. Our results show that Sur2 forms a subcomplex of the Mediator with two other subunits, TRAP/Med100 and 95. Knock-out of Sur2 prevents activation by E1A-CR3 and the mitogen-activated protein kinase-regulated ETS transcription factor Elk-1, but not by multiple other transcription factors. These results imply that specific activation domains stimulate transcription by binding to distinct Mediator subunits. Activation by E1A and Elk-1 requires recruitment of Mediator to a promoter by binding to its Sur2 subunit.

Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit.,Stevens JL, Cantin GT, Wang G, Shevchenko A, Shevchenko A, Berk AJ Science. 2002 Apr 26;296(5568):755-8. Epub 2002 Apr 4. PMID:11934987[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Boyer TG, Martin ME, Lees E, Ricciardi RP, Berk AJ. Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature. 1999 May 20;399(6733):276-9. PMID:10353252 doi:http://dx.doi.org/10.1038/20466
  2. Mo X, Kowenz-Leutz E, Xu H, Leutz A. Ras induces mediator complex exchange on C/EBP beta. Mol Cell. 2004 Jan 30;13(2):241-50. PMID:14759369
  3. Baek HJ, Kang YK, Roeder RG. Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly. J Biol Chem. 2006 Jun 2;281(22):15172-81. Epub 2006 Apr 4. PMID:16595664 doi:M601983200
  4. Stevens JL, Cantin GT, Wang G, Shevchenko A, Shevchenko A, Berk AJ. Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit. Science. 2002 Apr 26;296(5568):755-8. Epub 2002 Apr 4. PMID:11934987 doi:http://dx.doi.org/10.1126/science.1068943

6h02, resolution 2.80Å

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