7NGF
P2c-state of wild type human mitochondrial LONP1 protease with bound endogenous substrate protein and in presence of ATP/ADP mix
Summary for 7NGF
Entry DOI | 10.2210/pdb7ngf/pdb |
Related | 7NFY 7NG4 7NG5 7NGC 7NGL 7NGP 7NGQ 7OWA |
EMDB information | 12307 12308 12312 12313 12315 12316 12317 |
Descriptor | Lon protease homolog, mitochondrial, substrate protein chain:G, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total) |
Functional Keywords | human mitochondrial aaa+ protease, motor protein |
Biological source | Homo sapiens (Human) More |
Total number of polymer chains | 7 |
Total formula weight | 566991.71 |
Authors | Mohammed, I.,Schmitz, K.A.,Schenck, N.,Maier, T.,Abrahams, J.P. (deposition date: 2021-02-09, release date: 2021-04-28, Last modification date: 2024-07-10) |
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 Cited by 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: 35870450DOI: 10.1016/j.str.2022.06.006 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (5.6 Å) |
Structure validation
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