3TS9

Crystal Structure of the MDA5 Helicase Insert Domain

3TS9 の概要

• エントリーDOI: 10.2210/pdb3ts9/pdb
• 分子名称: Interferon-induced helicase C domain-containing protein 1, SULFATE ION (3 entities in total)
• 機能のキーワード: helix bundle, fancm helicase, super family 2 helicase, sf2 helicase, dexd/h helicase, rig-i-like helicase, antiviral protein, hydrolase
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm : Q8R5F7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16741.95

構造登録者

Berke, I.C.,Modis, Y. (登録日: 2011-09-12, 公開日: 2012-02-22, 最終更新日: 2024-02-28)

主引用文献

Berke, I.C.,Modis, Y.
MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA.
Embo J., 31:1714-1726, 2012

PubMed Abstract: Melanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm. RNA binding induces MDA5 to activate the signalling adaptor MAVS through interactions between the caspase recruitment domains (CARDs) of the two proteins. The molecular mechanism of MDA5 signalling is not well understood. Here, we show that MDA5 cooperatively binds short RNA ligands as a dimer with a 16-18-basepair footprint. A crystal structure of the MDA5 helicase-insert domain demonstrates an evolutionary relationship with the archaeal Hef helicases. In X-ray solution structures, the CARDs in unliganded MDA5 are flexible, and RNA binds on one side of an asymmetric MDA5 dimer, bridging the two subunits. On longer RNA, full-length and CARD-deleted MDA5 constructs assemble into ATP-sensitive filaments. We propose a signalling model in which the CARDs on MDA5-RNA filaments nucleate the assembly of MAVS filaments with the same polymeric geometry.

PubMed: 22314235
DOI: 10.1038/emboj.2012.19

実験手法

X-RAY DIFFRACTION (2.003 Å)