4IG8

Structural basis for cytosolic double-stranded RNA surveillance by human OAS1

4IG8 の概要

• エントリーDOI: 10.2210/pdb4ig8/pdb
• 分子名称: 2'-5'-oligoadenylate synthase 1, RNA (5'-R(*GP*GP*CP*UP*UP*UP*UP*GP*AP*CP*CP*UP*UP*UP*AP*UP*GP*C)-3'), RNA (5'-R(*GP*CP*AP*UP*AP*AP*AP*GP*GP*UP*CP*AP*AP*AP*AP*GP*CP*C)-3'), ... (6 entities in total)
• 機能のキーワード: nucleotidyl transferase, innate immune system double-stranded dsrna sensor rna polymerase, nucleotidyl transferase 2-5a synthetase, rnase l activator, double-stranded rna, cytosol, transferase-rna complex, transferase/rna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00973
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 52141.89

構造登録者

Donovan, J.,Korennykh, A. (登録日: 2012-12-16, 公開日: 2013-01-16, 最終更新日: 2024-02-28)

主引用文献

Donovan, J.,Dufner, M.,Korennykh, A.
Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1.
Proc.Natl.Acad.Sci.USA, 110:1652-1657, 2013

PubMed Abstract: The human sensor of double-stranded RNA (dsRNA) oligoadenylate synthetase 1 (hOAS1) polymerizes ATP into 2',5'-linked iso-RNA (2-5A) involved in innate immunity, cell cycle, and differentiation. We report the crystal structure of hOAS1 in complex with dsRNA and 2'-deoxy ATP at 2.7 Å resolution, which reveals the mechanism of cytoplasmic dsRNA recognition and activation of oligoadenylate synthetases. Human OAS1 recognizes dsRNA using a previously uncharacterized protein/RNA interface that forms via a conformational change induced by binding of dsRNA. The protein/RNA interface involves two minor grooves and has no sequence-specific contacts, with the exception of a single hydrogen bond between the -NH(2) group of nucleobase G17 and the carbonyl oxygen of serine 56. Using a biochemical readout, we show that hOAS1 undergoes more than 20,000-fold activation upon dsRNA binding and that canonical or GU-wobble substitutions produce dsRNA mutants that retain either full or partial activity, in agreement with the crystal structure. Ultimately, the binding of dsRNA promotes an elaborate conformational rearrangement in the N-terminal lobe of hOAS1, which brings residues D75, D77, and D148 into proximity and creates coordination geometry for binding of two catalytic Mg(2+) ions and ATP. The assembly of this critical active-site structure provides the gate that couples binding of dsRNA to the production and downstream functions of 2-5A.

PubMed: 23319625
DOI: 10.1073/pnas.1218528110

実験手法

X-RAY DIFFRACTION (2.7 Å)