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| Title | Antiviral signaling of a type III CRISPR-associated deaminase. |
|---|---|
| Journal, issue, pages | Science, Vol. 387, Issue 6736, Page eadr0393, Year 2025 |
| Publish date | Feb 21, 2025 |
Authors | Yutao Li / Zhaoxing Li / Purui Yan / Chenyang Hua / Jianping Kong / Wanqian Wu / Yurong Cui / Yan Duan / Shunxiang Li / Guanglei Li / Shunli Ji / Yijun Chen / Yucheng Zhao / Peng Yang / Chunyi Hu / Meiling Lu / Meirong Chen / Yibei Xiao / ![]() |
| 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 ...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. |
External links | Science / PubMed:39666823 |
| Methods | EM (single particle) |
| Resolution | 2.28 - 3.89 Å |
| Structure data | EMDB-39746: The structure of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated EMDB-39750, PDB-8z3p: EMDB-39752, PDB-8z3r: EMDB-39759, PDB-8z40: ![]() EMDB-39945: Focused map for area 1 of type III CRISPR-associated deaminase in complex cA4 ![]() EMDB-39951: Raw consensus map of type III CRISPR-associated deaminase in complex cA4 ![]() EMDB-39952: Focused map for area 2 of type III CRISPR-associated deaminase in complex cA4 ![]() EMDB-39953: Focused map for area 3 of type III CRISPR-associated deaminase in complex cA4 ![]() EMDB-39955: Focused map for area 1 of type III CRISPR-associated deaminase in complex cA6 and ATP ![]() EMDB-39965: Focused map for area 2 of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated ![]() EMDB-39966: Focused map for area 3 of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated ![]() EMDB-39967: Raw consensus map of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated ![]() EMDB-39968: Focused map for area 1 of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated ![]() EMDB-39969: Focused map for area 2 of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated ![]() EMDB-60045: Raw consensus map of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated |
| Chemicals | ![]() ChemComp-ZN: ![]() ChemComp-ATP: ![]() ChemComp-MG: ![]() ChemComp-LQJ: |
| Source |
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Keywords | IMMUNE SYSTEM / defense system / deaminase |
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