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Structure paper

TitleAntiviral signaling of a type III CRISPR-associated deaminase.
Journal, issue, pagesScience, Page eadr0393, Year 2024
Publish dateDec 12, 2024
AuthorsYutao 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 AbstractProkaryotes 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 ...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.
External linksScience / PubMed:39666823
MethodsEM (single particle)
Resolution2.28 - 3.89 Å
Structure data

39746

8z3k

EMDB-39746: The structure of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated
PDB-8z3k: The structure of type III CRISPR-associated deaminase in complex 2cA6-2ATP
Method: EM (single particle) / Resolution: 3.19 Å

39750

8z3p

EMDB-39750, PDB-8z3p:
The structure of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated
Method: EM (single particle) / Resolution: 3.4 Å

39752

8z3r

EMDB-39752, PDB-8z3r:
The structure of type III CRISPR-associated deaminase in complex cA4
Method: EM (single particle) / Resolution: 2.28 Å

39759

8z40

EMDB-39759, PDB-8z40:
The structure of type III CRISPR-associated deaminase apo form
Method: EM (single particle) / Resolution: 3.26 Å

EMDB-39945: Focused map for area 1 of type III CRISPR-associated deaminase in complex cA4
Method: EM (single particle) / Resolution: 2.63 Å

EMDB-39951: Raw consensus map of type III CRISPR-associated deaminase in complex cA4
Method: EM (single particle) / Resolution: 2.42 Å

EMDB-39952: Focused map for area 2 of type III CRISPR-associated deaminase in complex cA4
Method: EM (single particle) / Resolution: 2.61 Å

EMDB-39953: Focused map for area 3 of type III CRISPR-associated deaminase in complex cA4
Method: EM (single particle) / Resolution: 2.66 Å

EMDB-39955: Focused map for area 1 of type III CRISPR-associated deaminase in complex cA6 and ATP
Method: EM (single particle) / Resolution: 3.67 Å

EMDB-39965: Focused map for area 2 of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated
Method: EM (single particle) / Resolution: 3.89 Å

EMDB-39966: Focused map for area 3 of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated
Method: EM (single particle) / Resolution: 3.59 Å

EMDB-39967: Raw consensus map of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated
Method: EM (single particle) / Resolution: 3.34 Å

EMDB-39968: Focused map for area 1 of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated
Method: EM (single particle) / Resolution: 3.71 Å

EMDB-39969: Focused map for area 2 of type III CRISPR-associated deaminase in complex 2cA6 and 2ATP, partial activated
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-60045: Raw consensus map of type III CRISPR-associated deaminase in complex cA6 and ATP, fully activated
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-LQJ:
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

Source
  • limisphaera ngatamarikiensis (bacteria)
KeywordsIMMUNE SYSTEM / defense system / deaminase

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