8Z3R

The structure of type III CRISPR-associated deaminase in complex cA4

Summary for 8Z3R

• Entry DOI: 10.2210/pdb8z3r/pdb
• EMDB information: 39752
• Descriptor: Adenosine deaminase domain-containing protein, ZINC ION, 3'-O-[(R)-{[(2S,3aS,4S,6S,6aS)-6-(6-amino-9H-purin-9-yl)-2-hydroxy-2-oxotetrahydro-2H-2lambda~5~-furo[3,4-d][1,3,2]dioxaphosphol-4-yl]methoxy}(hydroxy)phosphoryl]adenosine (3 entities in total)
• Functional Keywords: defense system, deaminase, immune system
• Biological source: Limisphaera ngatamarikiensis
• Total number of polymer chains: 6
• Total formula weight: 429502.08

Authors

Chen, M.R.,Li, Z.X.,Xiao, Y.B. (deposition date: 2024-04-16, release date: 2024-12-25, Last modification date: 2025-07-23)

Primary citation

Li, Y.,Li, Z.,Yan, P.,Hua, C.,Kong, J.,Wu, W.,Cui, Y.,Duan, Y.,Li, S.,Li, G.,Ji, S.,Chen, Y.,Zhao, Y.,Yang, P.,Hu, C.,Lu, M.,Chen, M.,Xiao, Y.
Antiviral signaling of a type III CRISPR-associated deaminase.
Science, 387:eadr0393-eadr0393, 2025

PubMed Abstract: Prokaryotes have evolved diverse defense strategies against viral infection, including foreign nucleic acid degradation by CRISPR-Cas systems and DNA and RNA synthesis inhibition through nucleotide pool depletion. Here, we report an antiviral mechanism of type III CRISPR-Cas-regulated adenosine triphosphate (ATP) depletion in which ATP is converted into inosine triphosphate (ITP) by CRISPR-Cas-associated adenosine deaminase (CAAD) upon activation by either cA or cA, followed by hydrolysis into inosine monophosphate (IMP) by Nudix hydrolase, ultimately resulting in cell growth arrest. The cryo-electron microscopy structures of CAAD in its apo and activated forms, together with biochemical evidence, revealed how cA or cA binds to the CRISPR-associated Rossmann fold (CARF) domain and abrogates CAAD autoinhibition, inducing substantial conformational changes that reshape the structure of CAAD and induce its deaminase activity. Our results reveal the mechanism of a CRISPR-Cas-regulated ATP depletion antiviral strategy.

PubMed: 39666823
DOI: 10.1126/science.adr0393

Experimental method

ELECTRON MICROSCOPY (2.28 Å)