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-Structure paper
タイトル | Catalytic cycling of human mitochondrial Lon protease. |
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ジャーナル・号・ページ | Structure, Vol. 30, Issue 9, Page 1254-11268.e7, Year 2022 |
掲載日 | 2022年9月1日 |
著者 | Inayathulla Mohammed / Kai A Schmitz / Niko Schenck / Dimitrios Balasopoulos / Annika Topitsch / Timm Maier / Jan Pieter Abrahams / |
PubMed 要旨 | The mitochondrial Lon protease (LonP1) regulates mitochondrial health by removing redundant proteins from the mitochondrial matrix. We determined LonP1 in eight nucleotide-dependent conformational ...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. |
リンク | Structure / PubMed:35870450 |
手法 | EM (単粒子) |
解像度 | 3.8 - 15.0 Å |
構造データ | EMDB-12306, PDB-7nfy: EMDB-12307, PDB-7ng4: EMDB-12308, PDB-7ng5: EMDB-12312, PDB-7ngc: EMDB-12313, PDB-7ngf: EMDB-12315, PDB-7ngl: EMDB-12316, PDB-7ngp: EMDB-12317, PDB-7ngq: EMDB-13102, PDB-7oxo: |
化合物 | ChemComp-AGS: ChemComp-MG: ChemComp-ADP: ChemComp-ATP: |
由来 |
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キーワード | MOTOR PROTEIN / human mitochondrial AAA+ protease / protease / unfolds / hexamer / AAA+ protein / chaperone |