9MUO

Cryo-EM structure of CRISPR-associated cA4 bound Cat1 Pentagonal filament assembly in the presence of NAD analog BAD

Summary for 9MUO

• Entry DOI: 10.2210/pdb9muo/pdb
• EMDB information: 48639
• Descriptor: Cat1 (CRISPR-associated TIR 1), RNA (5'-R(P*AP*AP*AP*A)-3'), [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl [(2R,3S,4R,5S)-5-(3-carbamoylphenyl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate (non-preferred name) (3 entities in total)
• Functional Keywords: crispr, antiphage defense, adaptive immunity, filament, carf, tir, ca4, nad, adpr, nam, bad, antiviral protein
• Biological source: bacterium; More
• Total number of polymer chains: 6
• Total formula weight: 123808.54

Authors

Majumder, P.,Patel, D.J. (deposition date: 2025-01-14, release date: 2025-04-16, Last modification date: 2025-06-25)

Primary citation

Baca, C.F.,Majumder, P.,Hickling, J.H.,Patel, D.J.,Marraffini, L.A.
Cat1 forms filament networks to degrade NAD + during the type III CRISPR-Cas antiviral response.
Science, 388:eadv9045-eadv9045, 2025

PubMed Abstract: Type III CRISPR-Cas systems defend against viral infection in prokaryotes using an RNA-guided complex that recognizes foreign transcripts and synthesizes cyclic oligo-adenylate (cOA) messengers to activate CARF immune effectors. Here 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 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. Further, Cat1 filaments assemble into unique trigonal and pentagonal networks that enhance NAD degradation. Cat1 presents an unprecedented chemistry and higher-order protein assembly for the CRISPR-Cas response.

PubMed: 40208959
DOI: 10.1126/science.adv9045

Experimental method

ELECTRON MICROSCOPY (3.3 Å)