Nucleic-acid-triggered NADase activation of a short prokaryotic Argonaute. (https://www.nature.com/articles/s41586-023-06665-6)
These scientists wanted to understand how a certain protein called Argonaute (Ago) helps to protect cells from harmful genetic material. They studied a type of Ago protein called short pAgo, which was found in a tiny organism called Crenotalea thermophila.
To do this, the scientists used a special technique called cryo-electron microscopy to take pictures of the short pAgo protein and the other proteins it interacts with. They took pictures of the protein by freezing it very quickly and using a special microscope to see its structure.
The pictures showed that the short pAgo protein is made up of two parts: an Ago part and a TIR-APAZ part. The Ago part has two domains called MID and PIWI, while the TIR-APAZ part has several different domains. The scientists also found that the short pAgo protein can bind to a special type of genetic material called RNA-DNA duplex.
When the short pAgo protein binds to RNA-DNA duplex, it causes some changes in its structure. One part of the protein acts like a roadblock, preventing the RNA and DNA from going to their usual places. This causes the protein to form dimers, which means two short pAgo proteins come together. These dimers can then form a tetramer, which means four short pAgo proteins come together.
The scientists also discovered that the TIR domains in the protein can form special structures called dimers. These dimers help the protein to do its job of protecting cells from harmful genetic material.
Overall, this study helped the scientists understand how the short pAgo protein works to defend cells against harmful genetic material. This knowledge can be used to develop better ways of detecting and protecting against harmful DNA sequences.
Gao X., Shang K., Zhu K., Wang L., Mu Z., Fu X., Yu X., Qin B., Zhu H., Ding W., Cui S. Nucleic-acid-triggered NADase activation of a short prokaryotic Argonaute. Nature. 2024 Jan;625(7996):822-831. doi: 10.1038/s41586-023-06665-6. Epub 2023 Oct 2.