6MEV

Structure of JMJD6 bound to Mono-Methyl Arginine.

6MEV の概要

• エントリーDOI: 10.2210/pdb6mev/pdb
• 分子名称: Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6, 2-OXOGLUTARIC ACID, FE (III) ION, ... (5 entities in total)
• 機能のキーワード: jumonji, arginine, transcription, methyl, endopeptidase, exopeptidase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 322923.49

構造登録者

Lee, S.,Zhang, G. (登録日: 2018-09-07, 公開日: 2019-09-18, 最終更新日: 2025-04-02)

主引用文献

Lee, S.,Liu, H.,Hill, R.,Chen, C.,Hong, X.,Crawford, F.,Kingsley, M.,Zhang, Q.,Liu, X.,Chen, Z.,Lengeling, A.,Bernt, K.M.,Marrack, P.,Kappler, J.,Zhou, Q.,Li, C.Y.,Xue, Y.,Hansen, K.,Zhang, G.
JMJD6 cleaves MePCE to release positive transcription elongation factor b (P-TEFb) in higher eukaryotes.
Elife, 9:-, 2020

PubMed Abstract: More than 30% of genes in higher eukaryotes are regulated by promoter-proximal pausing of RNA polymerase II (Pol II). Phosphorylation of Pol II CTD by positive transcription elongation factor b (P-TEFb) is a necessary precursor event that enables productive transcription elongation. The exact mechanism on how the sequestered P-TEFb is released from the 7SK snRNP complex and recruited to Pol II CTD remains unknown. In this report, we utilize mouse and human models to reveal methylphosphate capping enzyme (MePCE), a core component of the 7SK snRNP complex, as the cognate substrate for Jumonji domain-containing 6 (JMJD6)'s novel proteolytic function. Our evidences consist of a crystal structure of JMJD6 bound to methyl-arginine, enzymatic assays of JMJD6 cleaving MePCE in vivo and in vitro, binding assays, and downstream effects of knockout and overexpression on Pol II CTD phosphorylation. We propose that JMJD6 assists bromodomain containing 4 (BRD4) to recruit P-TEFb to Pol II CTD by disrupting the 7SK snRNP complex.

PubMed: 32048991
DOI: 10.7554/eLife.53930

実験手法

X-RAY DIFFRACTION (2.6 Å)