Proteasomal conformation controls unfolding ability

What is it about?

The proteasome is a molecular machine inside all of our cells that unfolds and degrades proteins the cell doesn't want anymore. As part of the degradation process, the proteasome switches from a conformation or shape that can accept proteins to be degraded to a conformation better suited for pulling the substrates into a central degradation chamber. In this work we used a fluorescence technique to examine the proteasome's conformation and found that making changes to the proteasome that disfavor the pulling conformation also decrease the proteasome's ability to unfold and degrade substrates.

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Photo by Mila Di Bella on Unsplash

Photo by Mila Di Bella on Unsplash

Why is it important?

The proteasome is an important drug target in diseases ranging from cancer to neurodegeneration. Current drugs inhibit the proteasome. Controlling the proteasome's conformation might be a way to affect which proteins get degraded by the proteasome without completely inhibiting it.