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bioRxiv · 10.1101/2025.04.06.647259

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

Wassarman, D. R.·Pfaff, P.·Paulo, J. A.·Gygi, S. P.·Shokat, K. M.·Kranzusch, P. J.
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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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Wassarman, D. R., Pfaff, P., Paulo, J. A., Gygi, S. P., Shokat, K. M., Kranzusch, P. J.. 2025-04-06. Deazaguanylation is a nucleobase-protein conjugation required for type IV CBASS immunity. https://doi.org/10.1101/2025.04.06.647259

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