9JWA

Crystal Structure of Lon Bound to a Substrate.

Summary for 9JWA

• Entry DOI: 10.2210/pdb9jwa/pdb
• Descriptor: DUF1150 domain-containing protein, Lon protease (3 entities in total)
• Functional Keywords: lon protease, lara, regulator, caulobacter crescentus, hydrolase
• Biological source: Caulobacter vibrioides (strain ATCC 19089 / CIP 103742 / CB 15) (Caulobacter crescentus); More
• Total number of polymer chains: 4
• Total formula weight: 65366.53

Authors

Wang, H.J.,Kuan, Y.E.,Chang, C.I. (deposition date: 2024-10-10, release date: 2025-03-12, Last modification date: 2025-03-19)

Primary citation

Wang, H.J.,Kuan, Y.E.,Ho, M.R.,Chang, C.I.
Structural basis for the allosteric activation of Lon by the heat shock protein LarA.
Nat Commun, 16:2212-2212, 2025

PubMed 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 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 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.

PubMed: 40044692
DOI: 10.1038/s41467-025-57482-6

Experimental method

X-RAY DIFFRACTION (2.29 Å)