Structural basis for the allosteric activation of Lon by the heat shock protein LarA

Structural basis for the allosteric activation of Lon by the heat shock protein LarA

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Abstract Lon is a conserved AAA+ (ATPases associated with diverse cellular activities) proteolytic machine that plays a key regulatory role in cells under proteotoxic stress.Lon-mediated proteolysis can be stimulated by either the unfolded or specific protein substrates fox farms ocean forest ph accumulated under stress conditions.However, the molecular basis for this substrate-controlled proteolysis remains unclear.Here, we have found that the heat shock protein LarA, a recently discovered Lon substrate and allosteric activator, binds to the N-terminal domain (NTD) of Lon.

The crystal structure of the LarA-NTD complex shows that LarA g fuel spiderverse binds to a highly conserved groove in the NTD through the terminal aromatic residue of its C-terminal degron.Crystallographic and biochemical evidence further reveals that this binding exposes the hydrophobic core of LarA, which can bind a leucine residue and promote local protein unfolding.These results define the mechanistic role of the NTD in regulating Lon-mediated proteolysis in response to varying cellular conditions.