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PreprintCited by 9interferon and immune responsesBacteriophages and microbial interactionsDNA and Nucleic Acid Chemistry

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Deazaguanylation is a nucleobase-protein conjugation required for type IV CBASS immunity

Open access
Wassarman, Douglas R., Pfaff, Patrick, Paulo, Joao A., Gygi, Steven P., Shokat, Kevan M., Kranzusch, Philip J.·2025·Science
DOI 10.1101/2025.04.06.647259PMC PMC13044698

Preprint — published as 10.1126/science.adx6053 · Paper page

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Abstract

7-deazapurines are nucleobase analogs essential for nucleic acid modifications in nearly all cellular life. Here, we discover a role for 7-deazapurines in protein modification within type IV CBASS anti-phage defense and define functions for CBASS ancillary proteins Cap9 and Cap10 in nucleobase-protein conjugation. A structure of Cap10 reveals a tRNA transglycosylase-family enzyme remodeled to bind the modified N-terminus of a partner cGAS/DncV-like nucleotidyltransferase linked to a 7-amido-7-deazaguanine (NDG) nucleobase. The structure of Cap9 explains how this QueC-like enzyme co-opts a 7-deazapurine biosynthetic reaction mechanism for NDG conjugation. We demonstrate that Cap9, Cap10, and NDG conjugation are essential for host defense against phage infection. Our results define a previously unknown 7-deazapurine protein modification and explain how nucleobase biosynthetic machinery has been repurposed for antiviral immunity.

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Metadata

Authors
Wassarman, D. R., Pfaff, P., Paulo, J. A., Gygi, S. P., Shokat, K. M., & Kranzusch, P. J.
Affiliations
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
  • Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA
Corresponding author
Kranzusch, Philip J.
ORCID
Venue
Science
Publisher
openRxiv
Published
2025-04-06
Volume
389
Issue
6767
Pages
1347-1352
ISSN
0036-8075 (ISSN-L)
DOI
10.1101/2025.04.06.647259
PMC
PMC13044698
OpenAlex
W4414499149
Cited by
9
References
1
Citations by year
2026: 7 · 2025: 2
FWCI
3.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • National Science Foundation (P30GM133893, DE-SC0012704)
  • U.S. Department of Energy (DE‐SC0012704, KP1607011, SC0012704., P30GM133893)
  • Parker Institute for Cancer Immunotherapy
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (214278)
  • National Institutes of Health (GM97645, 1dp2gm146250-01)
  • Office of Science (DE-SC-0012704, SC0012704, KP1607011)
  • National Institute of General Medical Sciences (1DP2GM146250, 1DP2GM146250-01, DP2 GM146250, R01GM132129, GM97645, GM132129, P30GM133893, T32GM145460)
  • Biological and Environmental Research (DE-SC0012704, KP1607011)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
7-deazapurines, anti-phage defense, protein modification, phage resistance, host-virus interaction

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