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-Structure paper
タイトル | Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions. |
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ジャーナル・号・ページ | Sci Rep, Vol. 14, Issue 1, Page 9923, Year 2024 |
掲載日 | 2024年4月30日 |
著者 | Nina Kunová / Gabriela Ondrovičová / Jacob A Bauer / Veronika Krajčovičová / Matyáš Pinkas / Barbora Stojkovičová / Henrieta Havalová / Veronika Lukáčová / Lenka Kohútová / Július Košťan / Lucia Martináková / Peter Baráth / Jiří Nováček / Sebastian Zoll / Sami Kereϊche / Eva Kutejová / Vladimír Pevala / |
PubMed 要旨 | 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 ...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. |
リンク | Sci Rep / PubMed:38688959 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.88 - 8.47 Å |
構造データ | EMDB-16915, PDB-8ojl: EMDB-16923, PDB-8oka: EMDB-16970, PDB-8om7: EMDB-17213, PDB-8ovf: EMDB-17214, PDB-8ovg: |
化合物 | ChemComp-ADP: |
由来 |
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キーワード | HYDROLASE / Human mitochondrial AAA+ protease / motor protein |