Summary information and primary citation
- PDB-id
-
8wd8;
DSSR-derived features in text and
JSON formats
- Class
- DNA binding protein-DNA
- Method
- cryo-EM (2.9 Å)
- Summary
- cryo-EM structure of ttdago-guide DNA-target DNA
complex
- Reference
-
Wang L, Chen W, Zhang C, Xie X, Huang F, Chen M, Mao W,
Yu N, Wei Q, Ma L, Li Z (2024): "Molecular
mechanism for target recognition, dimerization, and
activation of Pyrococcus furiosus Argonaute."
Mol.Cell, 84, 675-686.e4. doi:
10.1016/j.molcel.2024.01.004.
- Abstract
- The Argonaute nuclease from the thermophilic archaeon
Pyrococcus furiosus (PfAgo) contributes to host defense and
represents a promising biotechnology tool. Here, we report
the structure of a PfAgo-guide DNA-target DNA ternary
complex at the cleavage-compatible state. The ternary
complex is predominantly dimerized, and the dimerization is
solely mediated by PfAgo at PIWI-MID, PIWI-PIWI, and PAZ-N
interfaces. Additionally, PfAgo accommodates a short 14-bp
guide-target DNA duplex with a wedge-type N domain and
specifically recognizes 5'-phosphorylated guide DNA. In
contrast, the PfAgo-guide DNA binary complex is monomeric,
and the engagement of target DNA with 14-bp complementarity
induces sufficient dimerization and activation of PfAgo,
accompanied by movement of PAZ and N domains. A closely
related Argonaute from Thermococcus thioreducens adopts a
similar dimerization configuration with an additional zinc
finger formed at the dimerization interface. Dimerization
of both Argonautes stabilizes the catalytic loops,
highlighting the important role of Argonaute dimerization
in the activation and target cleavage.
