2ky6
From Proteopedia
Structure of ARC92VBD/MED25ACID
Structural highlights
DiseaseMED25_HUMAN Charcot-Marie-Tooth disease type 2B2. The disease is caused by mutations affecting the gene represented in this entry.[1] FunctionMED25_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 PubMedThe human Mediator coactivator complex interacts with many transcriptional activators and facilitates recruitment of RNA polymerase II to promote target gene transcription. The MED25 subunit is a critical target of the potent herpes simplex 1 viral transcriptional activator VP16. Here we determine the solution structure of the MED25 VP16-binding domain (VBD) and define its binding site for the N-terminal portion of the VP16 transactivation domain (TADn). A hydrophobic furrow, formed by a beta-barrel and two alpha-helices in MED25 VBD, interacts tightly with VP16 TADn. Mutations in this furrow prevent binding of VP16 TAD to MED25 VBD and interfere with the ability of overexpressed MED25 VBD to inhibit VP16-dependent transcriptional activation in vivo. This detailed molecular understanding of transactivation by the benchmark activator VP16 could provide important insights into viral and cellular gene activation mechanisms. Structure of the VP16 transactivator target in the Mediator.,Milbradt AG, Kulkarni M, Yi T, Takeuchi K, Sun ZY, Luna RE, Selenko P, Naar AM, Wagner G Nat Struct Mol Biol. 2011 Apr;18(4):410-5. Epub 2011 Mar 6. PMID:21378963[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Milbradt AG | Naar AM | Selenko P | Sun ZJ | Takeuchi K | Wagner G
