4RWP

Crystal structure of porcine OAS1 in complex with dsRNA

4RWP の概要

• エントリーDOI: 10.2210/pdb4rwp/pdb
• 関連するPDBエントリー: 4RWN 4RWO 4RWQ
• 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*AP*A)-3'), RNA (5'-R(*UP*UP*CP*AP*UP*AP*AP*AP*GP*GP*UP*CP*AP*AP*AP*AP*GP*CP*C)-3'), ... (4 entities in total)
• 機能のキーワード: interferon-induced, dsrna-activated, transferase-rna complex, transferase/rna
• 由来する生物種: Sus scrofa (pigs,swine,wild boar); 詳細
• 細胞内の位置: Cytoplasm : Q29599
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 53365.59

構造登録者

Lohoefener, J.,Steinke, N.,Kay-Fedorov, P.,Baruch, P.,Nikulin, A.,Tishchenko, S.,Manstein, D.J.,Fedorov, R. (登録日: 2014-12-05, 公開日: 2015-05-20, 最終更新日: 2024-02-28)

主引用文献

Lohofener, J.,Steinke, N.,Kay-Fedorov, P.,Baruch, P.,Nikulin, A.,Tishchenko, S.,Manstein, D.J.,Fedorov, R.
The Activation Mechanism of 2'-5'-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity.
Structure, 23:851-862, 2015

PubMed Abstract: 2'-5'-Oligoadenylate synthetases (OASs) produce the second messenger 2'-5'-oligoadenylate, which activates RNase L to induce an intrinsic antiviral state. We report on the crystal structures of catalytic intermediates of OAS1 including the OAS1·dsRNA complex without substrates, with a donor substrate, and with both donor and acceptor substrates. Combined with kinetic studies of point mutants and the previously published structure of the apo form of OAS1, the new data suggest a sequential mechanism of OAS activation and show the individual roles of each component. They reveal a dsRNA-mediated push-pull effect responsible for large conformational changes in OAS1, the catalytic role of the active site Mg(2+), and the structural basis for the 2'-specificity of product formation. Our data reveal similarities and differences in the activation mechanisms of members of the OAS/cyclic GMP-AMP synthase family of innate immune sensors. In particular, they show how helix 3103-α5 blocks the synthesis of cyclic dinucleotides by OAS1.

PubMed: 25892109
DOI: 10.1016/j.str.2015.03.012

実験手法

X-RAY DIFFRACTION (2.25 Å)