7ZEV

Free form of extended Cyp33-RRM

7ZEV の概要

• エントリーDOI: 10.2210/pdb7zev/pdb
• 関連するPDBエントリー: 7ZEW 7ZEX 7ZEY 7ZEZ
• NMR情報: BMRB: 34724
• 分子名称: Peptidyl-prolyl cis-trans isomerase E (1 entity in total)
• 機能のキーワード: rrm, rna binding protein-structural protein complex, histone 3, h3k4me3, epigenetic, mll1 transcription regulation, infant leukemia, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13189.85

構造登録者

Blatter, M.,Allain, F.,Meylan, C. (登録日: 2022-03-31, 公開日: 2022-04-13, 最終更新日: 2024-06-19)

主引用文献

Blatter, M.,Meylan, C.,Clery, A.,Giambruno, R.,Nikolaev, Y.,Heidecker, M.,Solanki, J.A.,Diaz, M.O.,Gabellini, D.,Allain, F.H.
RNA binding induces an allosteric switch in Cyp33 to repress MLL1-mediated transcription.
Sci Adv, 9:eadf5330-eadf5330, 2023

PubMed Abstract: Mixed-lineage leukemia 1 (MLL1) is a transcription activator of the HOX family, which binds to specific epigenetic marks on histone H3 through its third plant homeodomain (PHD3) domain. Through an unknown mechanism, MLL1 activity is repressed by cyclophilin 33 (Cyp33), which binds to MLL1 PHD3. We determined solution structures of Cyp33 RNA recognition motif (RRM) free, bound to RNA, to MLL1 PHD3, and to both MLL1 and the histone H3 lysine N6-trimethylated. We found that a conserved α helix, amino-terminal to the RRM domain, adopts three different positions facilitating a cascade of binding events. These conformational changes are triggered by Cyp33 RNA binding and ultimately lead to MLL1 release from the histone mark. Together, our mechanistic findings rationalize how Cyp33 binding to MLL1 can switch chromatin to a transcriptional repressive state triggered by RNA binding as a negative feedback loop.

PubMed: 37075125
DOI: 10.1126/sciadv.adf5330

実験手法

SOLUTION NMR