Check out our recent publication in Biomolecules

Key points of the work:

• ATP is involved in the stabilization of the inner membrane YME1L protease

• When introduced to denaturants, YME1L undergoes transient unfolding, followed by refolding to a non-native conformation, upon removal of the denaturant.

• Subsequent refolding yields an incomplete and unique conformation, relative to the starting ensemble.

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Abstract:

ATP-dependent proteases are ubiquitous across all kingdoms of life and are critical to the maintenance of intracellular protein quality control. Enzymatic function of these enzymes requires structural stability under conditions that may drive instability and/or loss of function in potential protein substrates. Thus, these molecular machines must demonstrate greater stability than their substrates in order to insure continued function in essential quality control networks. We report here a role for ATP in the stabilization of the inner membrane YME1L protease. Semi-quantitative fluorescence data derived from protein unfolding experiments with urea reveal non-standard protein unfolding behavior that is dependent on [ATP]. Stopped-flow fluorescence experiments demonstrate using multiple fluorophore systems that YME1L undergoes transient unfolding, followed by refolding to a non-native conformation, prior to reaching equilibrium. Additional stopped-flow fluorescence experiments based on nucleotide binding and unfoldase activities predict that transient unfolding yields incomplete refolding of the starting ensemble. Taken together, these data clearly define the stress limits of an important mitochondrial protease.

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