7JL0

Cryo-EM structure of MDA5-dsRNA in complex with TRIM65 PSpry domain (Monomer)

7JL0 の概要

• エントリーDOI: 10.2210/pdb7jl0/pdb
• EMDBエントリー: 22368 22369 22370 22371
• 分子名称: RNA (5'-R(P*GP*AP*CP*UP*GP*AP*CP*UP*GP*AP*CP*UP*GP*A)-3'), RNA (5'-R(P*UP*CP*AP*GP*UP*CP*AP*GP*UP*CP*AP*GP*UP*C)-3'), Interferon-induced helicase C domain-containing protein 1, ... (8 entities in total)
• 機能のキーワード: innate immunity, ubiquitin e3 ligase, dsrna, rna helicase, trim family, hydrolase-immune system-rna complex, hydrolase/immune system/rna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 116075.35

構造登録者

Kato, K.,Ahmad, S.,Hur, S. (登録日: 2020-07-29, 公開日: 2020-12-09, 最終更新日: 2024-03-06)

主引用文献

Kato, K.,Ahmad, S.,Zhu, Z.,Young, J.M.,Mu, X.,Park, S.,Malik, H.S.,Hur, S.
Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases.
Mol.Cell, 81:599-613.e8, 2021

PubMed Abstract: RNA helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryoelectron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement may apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses suggest not only conserved substrates for TRIM proteins but also, unexpectedly, deep evolutionary connections between TRIM proteins and RNA helicases, linking ubiquitin and RNA biology throughout animal evolution.

PubMed: 33373584
DOI: 10.1016/j.molcel.2020.11.047

実験手法

ELECTRON MICROSCOPY (4.3 Å)