Structure of the poxvirus decapping enzyme D9 reveals its mechanism of cap recognition and catalysis

Peters, Jessica K.; Tibble, Ryan W.; Warminski, Marcin; Jemielity, Jacek; Gross, John D.

doi:10.1016/j.str.2022.02.012

Structure of the poxvirus decapping enzyme D9 reveals its mechanism of cap recognition and catalysis

Journal Article · Mon Mar 14 00:00:00 EDT 2022 · Structure

DOI:https://doi.org/10.1016/j.str.2022.02.012· OSTI ID:1981769

^[1]; ^[1]; Warminski, Marcin ^[2]; ^[2]; ^[1]

Univ. of California, San Francisco, CA (United States)
Univ. of Warsaw (Poland)

Poxviruses encode decapping enzymes that remove the protective 5' cap from both host and viral mRNAs to commit transcripts for decay by the cellular exonuclease Xrn1. Decapping by these enzymes is critical for poxvirus pathogenicity by means of simultaneously suppressing host protein synthesis and limiting the accumulation of viral double-stranded RNA (dsRNA), a trigger for antiviral responses. Here we present a high-resolution structural view of the vaccinia virus decapping enzyme D9. This Nudix enzyme contains a domain organization different from other decapping enzymes in which a three-helix bundle is inserted into the catalytic Nudix domain. The 5' mRNA cap is positioned in a bipartite active site at the interface of the two domains. Specificity for the methylated guanosine cap is achieved by stacking between conserved aromatic residues in a manner similar to that observed in canonical cap-binding proteins VP39, eIF4E, and CBP20, and distinct from eukaryotic decapping enzyme Dcp2.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1981769

Journal Information:: Structure, Journal Name: Structure Journal Issue: 5 Vol. 30; ISSN 0969-2126

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biochemistry & molecular biology
Biophysics
Cap recognition
Catalysis
Cell biology
Host shutoff
Innate immunity
Poxvirus decapping enzyme D9
Virus-host interactions
dsRNA decay
mRNA decay

Structure of the poxvirus decapping enzyme D9 reveals its mechanism of cap recognition and catalysis

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