Unraveling a Protein that May Inspire a New Biotechnology Tool
Published:08 Nov.2023    Source:Ohio State University
Scientists have unraveled the step-by-step activation process of a protein with a deep evolutionary history in all domains of life, opening the door to harnessing its functions for use as a biotechnology tool. The protein belongs to the "superfamily" of Argonaute proteins, which previous research has suggested to be involved in gene silencing, a fundamental process known as RNA interference.
In this work, the research team focused on a protein called SPARTA, a short prokaryotic Argonaute (also referred to as Ago), specifically building upon other studies that showed this protein enables Maribacter polysiphoniae bacteria to program their death when they detect a plasmid invasion -- when external DNA segments are trying to insert themselves to change bacterial properties. Ago proteins in eukaryotes are known to remain as simple molecules throughout activation, with the ability to bind only to other simple molecules. They also are established as participants in RNA interference, an evolutionary strategy to inhibit the expression of specific genes that may represent a threat to cell survival. SPARTA, on the other hand, lacks certain structures that are needed to facilitate RNA interference. And though it starts out as a simple molecule like long prokaryotic and eukaryotic Agos, the activation similarities end there. Using cryogenic electron microscopy, researchers identified SPARTA's next steps: After it binds to RNA or DNA, it goes through numerous changes, eventually assembling into a larger multi-unit molecular complex.
All of this points to the fact that oligomerization -- the methodical conversion of simple molecules into molecular complexes -- is an essential part of activating short prokaryotic Argonaute proteins. The possibilities envisioned by Fu's lab include engineering short prokaryotic Agos that could help cells detect threats, or that could trigger molecules that threaten healthy cells to bring on their own death.