2l6u

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Solution NMR Structure of Med25(391-543) Comprising the Activator-Interacting Domain (ACID) of Human Mediator Subuniti 25. Northeast Structural Genomics Consortium Target HR6188A

Structural highlights

2l6u is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MED25_HUMAN Charcot-Marie-Tooth disease type 2B2. The disease is caused by mutations affecting the gene represented in this entry.[1]

Function

MED25_HUMAN 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 preinitiation complex with RNA polymerase II and the general transcription factors. Required for RARA/RXRA-mediated transcription.[2] [3] [4]

Publication Abstract from PubMed

The solution NMR structure of protein MED25(391-543), comprising the activator interacting domain (ACID) of subunit 25 of the human mediator, is presented along with the measurement of polypeptide backbone heteronuclear (15)N-{(1)H} NOEs to identify fast internal motional modes. This domain interacts with the acidic transactivation domains of Herpes simplex type 1 (HSV-1) protein VP16 and the Varicella-zoster virus (VZV) major transactivator protein IE62, which initiate transcription of viral genes. The structure is similar to the beta-barrel domains of the human protein Ku and the SPOC domain of human protein SHARP, and provides a starting point to understand the structural biology of initiation of HSV-1 and VZV gene activation. Homology models built for the two ACID domains of the prostate tumor overexpressed (PTOV1) protein using the structure of MED25(391-543) as a template suggest that differential biological activities of the ACID domains in MED25 and PTOV1 arise from modulation of quite similar protein-protein interactions by variable residues grouped around highly conserved charged surface areas.

Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25.,Eletsky A, Ruyechan WT, Xiao R, Acton TB, Montelione GT, Szyperski T J Struct Funct Genomics. 2011 Sep;12(3):159-66. Epub 2011 Jul 23. PMID:21785987[5]

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

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Citations
3 reviews cite this structure
A structural perspective on Mediator function.
Larivière et al. (2012)
2 more
9 other articles
No citations found

See Also

References

  1. ↑ Leal A, Huehne K, Bauer F, Sticht H, Berger P, Suter U, Morera B, Del Valle G, Lupski JR, Ekici A, Pasutto F, Endele S, Barrantes R, Berghoff C, Berghoff M, Neundorfer B, Heuss D, Dorn T, Young P, Santolin L, Uhlmann T, Meisterernst M, Sereda MW, Stassart RM, Meyer zu Horste G, Nave KA, Reis A, Rautenstrauss B. Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models. Neurogenetics. 2009 Oct;10(4):275-87. doi: 10.1007/s10048-009-0183-3. Epub 2009, Mar 17. PMID:19290556 doi:http://dx.doi.org/10.1007/s10048-009-0183-3
  2. ↑ Mittler G, Stuhler T, Santolin L, Uhlmann T, Kremmer E, Lottspeich F, Berti L, Meisterernst M. A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J. 2003 Dec 15;22(24):6494-504. PMID:14657022 doi:http://dx.doi.org/10.1093/emboj/cdg619
  3. ↑ Yang F, DeBeaumont R, Zhou S, Naar AM. The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator. Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2339-44. PMID:14983011
  4. ↑ Lee HK, Park UH, Kim EJ, Um SJ. MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation. EMBO J. 2007 Aug 8;26(15):3545-57. Epub 2007 Jul 19. PMID:17641689 doi:http://dx.doi.org/7601797
  5. ↑ Eletsky A, Ruyechan WT, Xiao R, Acton TB, Montelione GT, Szyperski T. Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25. J Struct Funct Genomics. 2011 Sep;12(3):159-66. Epub 2011 Jul 23. PMID:21785987 doi:10.1007/s10969-011-9115-1

Contents


PDB ID 2l6u

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