1XC5

Solution Structure of the SMRT Deacetylase Activation Domain

1XC5 の概要

• エントリーDOI: 10.2210/pdb1xc5/pdb
• NMR情報: BMRB: 6286
• 分子名称: Nuclear receptor corepressor 2 (1 entity in total)
• 機能のキーワード: four-helix structure, three-helix triangle, transcription corepressor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9Y618
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8578.96

構造登録者

Codina, A.,Love, J.D.,Li, Y.,Lazar, M.A.,Neuhaus, D.,Schwabe, J.W.R. (登録日: 2004-09-01, 公開日: 2005-05-03, 最終更新日: 2024-05-29)

主引用文献

Codina, A.,Love, J.D.,Li, Y.,Lazar, M.A.,Neuhaus, D.,Schwabe, J.W.R.
Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors
Proc.Natl.Acad.Sci.Usa, 102:6009-6014, 2005

PubMed Abstract: SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that play an essential role in the regulation of development and metabolism. This role is achieved, in part, through the recruitment of a key histone deacetylase (HDAC3), which is itself indispensable for cell viability. The assembly of HDAC3 with the deacetylase activation domain (DAD) of SMRT and NCoR is required for activation of the otherwise inert deacetylase. The DAD comprises an N-terminal DAD-specific motif and a C-terminal SANT (SWI3/ADA2/NCoR/TFIIIB)-like domain. We report here the solution structure of the DAD from SMRT, which reveals a four-helical structure. The DAD differs from the SANT (and MYB) domains in that (i) it has an additional N-terminal helix and (ii) there is a notable hydrophobic groove on the surface of the domain. Structure-guided mutagenesis, combined with interaction assays, showed that residues in the vicinity of the hydrophobic groove are required for interaction with (and hence activation of) HDAC3. Importantly, one surface-exposed lysine is required for activation of HDAC3, but not for interaction. This lysine may play a uniquely important role in the mechanism of activating HDAC3.

PubMed: 15837933
DOI: 10.1073/pnas.0500299102

実験手法

SOLUTION NMR