6L54

Structure of SMG189

6L54 の概要

• エントリーDOI: 10.2210/pdb6l54/pdb
• EMDBエントリー: 0837
• 分子名称: Serine/threonine-protein kinase SMG1, Protein SMG8, Protein SMG9, ... (5 entities in total)
• 機能のキーワード: smg189, cryo-em, nonsense-mediated mrna decay, transferase-transcription complex, transferase/transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 579057.68

構造登録者

Xu, Y.,Qi, Y. (登録日: 2019-10-22, 公開日: 2020-04-15, 最終更新日: 2024-03-27)

主引用文献

Zhu, L.,Li, L.,Qi, Y.,Yu, Z.,Xu, Y.
Cryo-EM structure of SMG1-SMG8-SMG9 complex.
Cell Res., 29:1027-1034, 2019

PubMed Abstract: Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of the stress response. The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism. Here, we determined the cryo-EM structures of human SMG1 at 3.6 Å resolution and the SMG1-SMG8-SMG9 complex at 3.4 Å resolution, respectively. SMG8 has a C-terminal kinase inhibitory domain (KID), which covers the catalytic pocket and inhibits the kinase activity of SMG1. Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8-SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity. Thus, our structural and biochemical analyses provide a mechanistic understanding of SMG1-SMG8-SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity.

PubMed: 31729466
DOI: 10.1038/s41422-019-0255-3

実験手法

ELECTRON MICROSCOPY (3.43 Å)