8Z3P

The structure of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated

Summary for 8Z3P

• Entry DOI: 10.2210/pdb8z3p/pdb
• EMDB information: 39750
• Descriptor: RNA (5'-R(P*AP*AP*AP*AP*AP*A)-3'), Adenosine deaminase domain-containing protein, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: defense system, deaminase, immune system
• Biological source: Limisphaera ngatamarikiensis; More
• Total number of polymer chains: 9
• Total formula weight: 428673.58

Authors

Chen, M.R.,Li, Z.X.,Xiao, Y.B. (deposition date: 2024-04-15, release date: 2024-12-25, Last modification date: 2025-03-05)

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, such as foreign nucleic acid degradation by CRISPR-Cas systems and DNA/RNA synthesis inhibition via nucleotide pool depletion. Here, we report an antiviral mechanism of type III CRISPR-Cas-regulated ATP depletion, where ATP is converted into ITP by CRISPR-Cas-associated adenosine deaminase (CAAD) upon activation by either cA or cA, followed by hydrolysis into 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/cA binds to the 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 (3.4 Å)