Recent research from The Ohio State University has revealed the step-by-step activation process of Argonaute proteins, potentially unlocking their use as a biotechnology tool. By utilizing cryogenic electron microscopy researchers analyzed the steps that lead the protein to ultimately be able to program its own cell death when threatened by bacteria.
In the study, published in Nature, the researchers analyzed an Argonaute protein called SPARTA. SPARTA is a short prokaryotic Argonaute (Ago for short) that in other studies has been identified as being responsible for Maribacter polysiphoniae bacteria's ability to program their own cell death when a plasmid invasion is detected. Ago proteins remain as simple molecules throughout activation and are part of an evolutionary strategy to inhibit the expression of genes that may reduce cell survival.
Using cryogenic electron microscopy, the researchers found that after SPARTA binds to RNA or DNA numerous changes occur eventually leading to it assembling into a large multi-unit molecular complex. Further analysis led to the discovery that these changes were necessary to ultimately be able to program the cell's death when it was threatened. This ultimately means that oligomerization plays a critical role in the activation of short prokaryotic Argonaute proteins.
"When we talk about one protein that is expressed everywhere, in all organisms, we know this protein is inherently important, even if we don't yet know all of its specific functions," said Zhangfei Shen, a postdoctoral scholar at The Ohio State University. "Now that we know not just that it is oligomerized, but how it is oligomerized, and captured the intermediate states it is in during oligomerization, we've made good progress toward developing this protein as a tool."
The researchers envision these findings being used to engineer short prokaryotic Agos as a biotechnology tool to help detect threats and even trigger targeted molecules to bring on their own death before they can be a threat to healthy cells.