Cat1 forms filament networks to degrade NAD(+) during the type III CRISPR-Cas antiviral response Journal Article
| Authors: | Baca, C. F.; Majumder, P.; Hickling, J. H.; Patel, D. J.; Marraffini, L. A. |
| Article Title: | Cat1 forms filament networks to degrade NAD(+) during the type III CRISPR-Cas antiviral response |
| Abstract: | Type III CRISPR-Cas systems defend against viral infection in prokaryotes by using an RNA-guided complex that recognizes foreign transcripts and synthesizes cyclic oligoadenylate (cOA) messengers to activate CRISPR-associated Rossmann-fold (CARF) immune effectors. In this study, we investigated a protein containing a CARF domain-fused Toll/interleukin-1 receptor (TIR) domain, Cat1. We found that Cat1 provides immunity by cleaving and depleting oxidized nicotinamide adenine dinucleotide (NAD+) molecules from the infected host, inducing a growth arrest that prevents viral propagation. Cat1 forms dimers that stack upon each other to generate long filaments that are maintained by bound cOA ligands, with stacked TIR domains forming the NAD+ cleavage catalytic sites. Furthermore, Cat1 filaments assemble into distinct trigonal and pentagonal networks that enhance NAD+ degradation. Cat1 presents an unprecedented chemistry and higher-order protein assembly for the CRISPR-Cas response. |
| Keywords: | genetics; protein domain; metabolism; chemistry; protein multimerization; catalytic domain; nad; nicotinamide adenine dinucleotide; enzyme active site; protein domains; crispr-associated proteins; adenine nucleotides; adenine nucleotide; crispr associated protein; crispr cas system; crispr-cas systems |
| Journal Title: | Science |
| Volume: | 388 |
| Issue: | 6752 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2025-06-12 |
| Start Page: | eadv9045 |
| Language: | English |
| DOI: | 10.1126/science.adv9045 |
| PUBMED: | 40208959 |
| PROVIDER: | scopus |
| PMCID: | PMC12162218 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Puja Majumder and Dinshaw Patel -- Source: Scopus |
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