 |
PDBsum entry 4o1o
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase,hydrolase
|
PDB id
|
|
|
|
4o1o
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Dimeric structure of pseudokinase rnase l bound to 2-5a reveals a basis for interferon-Induced antiviral activity.
|
|
|
Authors
|
|
H.Huang,
E.Zeqiraj,
B.Dong,
B.K.Jha,
N.M.Duffy,
S.Orlicky,
N.Thevakumaran,
M.Talukdar,
M.C.Pillon,
D.F.Ceccarelli,
L.C.Wan,
Y.C.Juang,
D.Y.Mao,
C.Gaughan,
M.A.Brinton,
A.A.Perelygin,
I.Kourinov,
A.Guarné,
R.H.Silverman,
F.Sicheri.
|
|
|
Ref.
|
|
Mol Cell, 2014,
53,
221-234.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
