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PDBsum entry 7k0r
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Viral protein
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PDB id
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7k0r
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References listed in PDB file
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Key reference
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Title
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Cryo-Em structures of the sars-Cov-2 endoribonuclease nsp15 reveal insight into nuclease specificity and dynamics.
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Authors
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M.C.Pillon,
M.N.Frazier,
L.B.Dillard,
J.G.Williams,
S.Kocaman,
J.M.Krahn,
L.Perera,
C.K.Hayne,
J.Gordon,
Z.D.Stewart,
M.Sobhany,
L.J.Deterding,
A.L.Hsu,
V.P.Dandey,
M.J.Borgnia,
R.E.Stanley.
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Ref.
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Nat Commun, 2021,
12,
636.
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PubMed id
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Abstract
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Nsp15, a uridine specific endoribonuclease conserved across coronaviruses,
processes viral RNA to evade detection by host defense systems. Crystal
structures of Nsp15 from different coronaviruses have shown a common hexameric
assembly, yet how the enzyme recognizes and processes RNA remains poorly
understood. Here we report a series of cryo-EM reconstructions of SARS-CoV-2
Nsp15, in both apo and UTP-bound states. The cryo-EM reconstructions, combined
with biochemistry, mass spectrometry, and molecular dynamics, expose molecular
details of how critical active site residues recognize uridine and facilitate
catalysis of the phosphodiester bond. Mass spectrometry revealed the
accumulation of cyclic phosphate cleavage products, while analysis of the apo
and UTP-bound datasets revealed conformational dynamics not observed by crystal
structures that are likely important to facilitate substrate recognition and
regulate nuclease activity. Collectively, these findings advance understanding
of how Nsp15 processes viral RNA and provide a structural framework for the
development of new therapeutics.
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