Summary for 8OM7
| Entry DOI | 10.2210/pdb8om7/pdb |
| Related | 8OJL 8OKA |
| EMDB information | 16970 |
| Descriptor | Lon protease homolog, mitochondrial, ADENOSINE-5'-DIPHOSPHATE (2 entities in total) |
| Functional Keywords | human mitochondrial aaa+ protease, motor protein, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 6 |
| Total formula weight | 591557.94 |
| Authors | Kereiche, S.,Bauer, J.A.,Matyas, P.,Novacek, J.,Kutejova, E. (deposition date: 2023-03-31, release date: 2024-04-10, Last modification date: 2024-05-15) |
| Primary citation | Kunova, N.,Ondrovicova, G.,Bauer, J.A.,Krajcovicova, V.,Pinkas, M.,Stojkovicova, B.,Havalova, H.,Lukacova, V.,Kohutova, L.,Kostan, J.,Martinakova, L.,Barath, P.,Novacek, J.,Zoll, S.,Kereiche, S.,Kutejova, E.,Pevala, V. Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions. Sci Rep, 14:9923-9923, 2024 Cited by PubMed Abstract: Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria. PubMed: 38688959DOI: 10.1038/s41598-024-60030-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.74 Å) |
Structure validation
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