7OXO

human LonP1, R-state, incubated in AMPPCP

Summary for 7OXO

• Entry DOI: 10.2210/pdb7oxo/pdb
• Related: 7nfy 7ng4 7ng5 7ngc 7ngf 7ngl 7ngp 7ngq
• EMDB information: 13102
• Descriptor: Lon protease homolog, mitochondrial, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• Functional Keywords: protease, chaperone, motor protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 642375.46

Authors

Abrahams, J.P.,Mohammed, I.,Schmitz, K.A.,Schenck, N.,Maier, T. (deposition date: 2021-06-22, release date: 2021-12-22, Last modification date: 2024-07-17)

Primary citation

Mohammed, I.,Schmitz, K.A.,Schenck, N.,Balasopoulos, D.,Topitsch, A.,Maier, T.,Abrahams, J.P.
Catalytic cycling of human mitochondrial Lon protease.
Structure, 30:1254-1268.e7, 2022

PubMed Abstract: The mitochondrial Lon protease (LonP1) regulates mitochondrial health by removing redundant proteins from the mitochondrial matrix. We determined LonP1 in eight nucleotide-dependent conformational states by cryoelectron microscopy (cryo-EM). The flexible assembly of N-terminal domains had 3-fold symmetry, and its orientation depended on the conformational state. We show that a conserved structural motif around T803 with a high similarity to the trypsin catalytic triad is essential for proteolysis. We show that LonP1 is not regulated by redox potential, despite the presence of two conserved cysteines at disulfide-bonding distance in its unfoldase core. Our data indicate how sequential ATP hydrolysis controls substrate protein translocation in a 6-fold binding change mechanism. Substrate protein translocation, rather than ATP hydrolysis, is a rate-limiting step, suggesting that LonP1 is a Brownian ratchet with ATP hydrolysis preventing translocation reversal. 3-fold rocking motions of the flexible N-domain assembly may assist thermal unfolding of the substrate protein.

PubMed: 35870450
DOI: 10.1016/j.str.2022.06.006

Experimental method

ELECTRON MICROSCOPY (3.9 Å)