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-Structure paper
タイトル | Structure and assembly of the mammalian mitochondrial supercomplex CIIICIV. |
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ジャーナル・号・ページ | Nature, Vol. 598, Issue 7880, Page 364-367, Year 2021 |
掲載日 | 2021年10月6日 |
著者 | Irene Vercellino / Leonid A Sazanov / |
PubMed 要旨 | The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes, whose precise role is ...The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes, whose precise role is debated. Supercomplexes CIIICIV (refs. ), CICIII (ref. ) and CICIIICIV (respirasome) exist in mammals, but in contrast to CICIII and the respirasome, to date the only known eukaryotic structures of CIIICIV come from Saccharomyces cerevisiae and plants, which have different organization. Here we present the first, to our knowledge, structures of mammalian (mouse and ovine) CIIICIV and its assembly intermediates, in different conformations. We describe the assembly of CIIICIV from the CIII precursor to the final CIIICIV conformation, driven by the insertion of the N terminus of the assembly factor SCAF1 (ref. ) deep into CIII, while its C terminus is integrated into CIV. Our structures (which include CICIII and the respirasome) also confirm that SCAF1 is exclusively required for the assembly of CIIICIV and has no role in the assembly of the respirasome. We show that CIII is asymmetric due to the presence of only one copy of subunit 9, which straddles both monomers and prevents the attachment of a second copy of SCAF1 to CIII, explaining the presence of one copy of CIV in CIIICIV in mammals. Finally, we show that CIII and CIV gain catalytic advantage when assembled into the supercomplex and propose a role for CIIICIV in fine tuning the efficiency of electron transfer in the electron transport chain. |
リンク | Nature / PubMed:34616041 |
手法 | EM (単粒子) |
解像度 | 2.6 - 3.6 Å |
構造データ | EMDB-12702, PDB-7o37: EMDB-12703, PDB-7o3c: EMDB-12705, PDB-7o3e: EMDB-12706, PDB-7o3h: |
化合物 | ChemComp-3PE: ChemComp-CDL: ChemComp-HEM: ChemComp-HEC: ChemComp-FES: ChemComp-PC1: ChemComp-TGL: ChemComp-CU: ChemComp-NA: ChemComp-HEA: ChemComp-MG: ChemComp-CUA: ChemComp-ZN: |
由来 |
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キーワード | MEMBRANE PROTEIN / mitochondria / respiratory chain / supercomplex / OXIDOREDUCTASE / complex III / complex IV |