Dimeric Structure of Pseudokinase RNase L Bound to 2-5A Reveals a Basis for Interferon-Induced Antiviral Activity

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