4O1P

Crystal Structure of RNase L in complex with 2-5A and AMP-PNP

4O1P の概要

• エントリーDOI: 10.2210/pdb4o1p/pdb
• 関連するPDBエントリー: 4O1O
• 分子名称: Ribonuclease L, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: ankyrin repeat-kinase-rnase, rna cleavage, 2-5a, transferase, hydrolase
• 由来する生物種: Sus scrofa (pig)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 332192.94

構造登録者

Huang, H.,Zeqiraj, E.,Ceccarelli, D.F.,Sicheri, F. (登録日: 2013-12-16, 公開日: 2014-02-05, 最終更新日: 2023-09-20)

主引用文献

Huang, H.,Zeqiraj, E.,Dong, B.,Jha, B.K.,Duffy, N.M.,Orlicky, S.,Thevakumaran, N.,Talukdar, M.,Pillon, M.C.,Ceccarelli, D.F.,Wan, L.C.,Juang, Y.C.,Mao, D.Y.,Gaughan, C.,Brinton, M.A.,Perelygin, A.A.,Kourinov, I.,Guarne, A.,Silverman, R.H.,Sicheri, F.
Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity.
Mol.Cell, 53:221-234, 2014

PubMed Abstract: RNase L is an ankyrin repeat domain-containing dual endoribonuclease-pseudokinase that is activated by unusual 2,'5'-oligoadenylate (2-5A) second messengers and which impedes viral infections in higher vertebrates. Despite its importance in interferon-regulated antiviral innate immunity, relatively little is known about its precise mechanism of action. Here we present a functional characterization of 2.5 Å and 3.25 Å X-ray crystal and small-angle X-ray scattering structures of RNase L bound to a natural 2-5A activator with and without ADP or the nonhydrolysable ATP mimetic AMP-PNP. These studies reveal how recognition of 2-5A through interactions with the ankyrin repeat domain and the pseudokinase domain, together with nucleotide binding, imposes a rigid intertwined dimer configuration that is essential for RNase catalytic and antiviral functions. The involvement of the pseudokinase domain of RNase L in 2-5A sensing, nucleotide binding, dimerization, and ribonuclease functions highlights the evolutionary adaptability of the eukaryotic protein kinase fold.

PubMed: 24462203
DOI: 10.1016/j.molcel.2013.12.025

実験手法

X-RAY DIFFRACTION (2.5 Å)