3U5M

Crystal structure of TRIM33 PHD-Bromo in the free state

3U5M の概要

• エントリーDOI: 10.2210/pdb3u5m/pdb
• 関連するPDBエントリー: 3U5N 3U5O 3U5P
• 分子名称: E3 ubiquitin-protein ligase TRIM33, ZINC ION, CALCIUM ION (3 entities in total)
• 機能のキーワード: trim33, phd, bromodomain, tgf-beta, epigenetics, histone, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9UPN9
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 288013.90

構造登録者

Wang, Z.,Patel, D.J. (登録日: 2011-10-11, 公開日: 2012-01-18, 最終更新日: 2023-09-13)

主引用文献

Xi, Q.,Wang, Z.,Zaromytidou, A.I.,Zhang, X.H.,Chow-Tsang, L.F.,Liu, J.X.,Kim, H.,Barlas, A.,Manova-Todorova, K.,Kaartinen, V.,Studer, L.,Mark, W.,Patel, D.J.,Massague, J.
A poised chromatin platform for TGF-beta access to master regulators
Cell(Cambridge,Mass.), 147:1511-1524, 2011

PubMed Abstract: Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-β signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compacting factor HP1γ, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.

PubMed: 22196728
DOI: 10.1016/j.cell.2011.11.032

実験手法

X-RAY DIFFRACTION (3.08 Å)