6H61

CryoEM structure of the MDA5-dsRNA filament with 89 degree twist and without nucleotide

6H61 の概要

• エントリーDOI: 10.2210/pdb6h61/pdb
• 関連するPDBエントリー: 6G19 6G1S 6G1X 6GJZ 6GKH 6GKM
• EMDBエントリー: 0012 0023 0024 0143 4338 4340 4341
• 分子名称: Interferon-induced helicase C domain-containing protein 1, RNA (5'-R(P*UP*CP*CP*AP*UP*GP*CP*GP*CP*AP*UP*GP*AP*CP*G)-3'), RNA (5'-R(P*CP*GP*UP*CP*AP*UP*GP*CP*GP*CP*AP*UP*GP*GP*A)-3'), ... (4 entities in total)
• 機能のキーワード: protein-rna complex, helical filament, atpase, innate immune receptor, immune system
• 由来する生物種: Mus musculus (House Mouse); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 123855.69

構造登録者

Yu, Q.,Qu, K.,Modis, Y. (登録日: 2018-07-25, 公開日: 2018-11-21, 最終更新日: 2024-05-15)

主引用文献

Yu, Q.,Qu, K.,Modis, Y.
Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis.
Mol. Cell, 72:999-1012.e6, 2018

PubMed Abstract: Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type I interferon signaling platform. Here, we determined cryoelectron microscopy (cryo-EM) structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs at resolutions sufficient to build and refine atomic models. The structures identify the filament-forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.

PubMed: 30449722
DOI: 10.1016/j.molcel.2018.10.012

実験手法

ELECTRON MICROSCOPY (4.02 Å)