4G8K

Intact sensor domain of human RNase L in the inactive signaling state

4G8K の概要

• エントリーDOI: 10.2210/pdb4g8k/pdb
• 関連するPDBエントリー: 4G8L
• 分子名称: 2-5A-dependent ribonuclease (2 entities in total)
• 機能のキーワード: ankyrin-repeat domain, single-stranded rna, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q05823
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74288.61

構造登録者

Han, Y.,Whitney, G.,Donovan, J.,Korennykh, A. (登録日: 2012-07-23, 公開日: 2012-10-31, 最終更新日: 2023-09-13)

主引用文献

Han, Y.,Whitney, G.,Donovan, J.,Korennykh, A.
Innate Immune Messenger 2-5A Tethers Human RNase L into Active High-Order Complexes.
Cell Rep, 2:902-913, 2012

PubMed Abstract: 2',5'-linked oligoadenylates (2-5As) serve as conserved messengers of pathogen presence in the mammalian innate immune system. 2-5As induce self-association and activation of RNase L, which cleaves cytosolic RNA and promotes the production of interferons (IFNs) and cytokines driven by the transcription factors IRF-3 and NF-κB. We report that human RNase L is activated by forming high-order complexes, reminiscent of the mode of activation of the phylogenetically related transmembrane kinase/RNase Ire1 in the unfolded protein response. We describe crystal structures determined at 2.4 Å and 2.8 Å resolution, which show that two molecules of 2-5A at a time tether RNase L monomers via the ankyrin-repeat (ANK) domain. Each ANK domain harbors two distinct sites for 2-5A recognition that reside 50 Å apart. These data reveal a function for the ANK domain as a 2-5A-sensing homo-oligomerization device and describe a nonlinear, ultrasensitive regulation in the 2-5A/RNase L system poised for amplification of the IFN response.

PubMed: 23084743
DOI: 10.1016/j.celrep.2012.09.004

実験手法

X-RAY DIFFRACTION (2.4 Å)