8E9H

Mycobacterial respiratory complex I, fully-inserted quinone

8E9H の概要

• エントリーDOI: 10.2210/pdb8e9h/pdb
• EMDBエントリー: 27964
• 分子名称: Two-component system response regulator, NADH-quinone oxidoreductase subunit H, NADH-quinone oxidoreductase subunit J, ... (22 entities in total)
• 機能のキーワード: complex, oxidative phosphorylation, nadh-quinone oxidoreductase, iron-sulfur protein, membrane protein
• 由来する生物種: Mycolicibacterium smegmatis MC2 155; 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 563687.42

構造登録者

Liang, Y.,Rubinstein, J.L. (登録日: 2022-08-26, 公開日: 2022-10-12, 最終更新日: 2023-04-05)

主引用文献

Liang, Y.,Plourde, A.,Bueler, S.A.,Liu, J.,Brzezinski, P.,Vahidi, S.,Rubinstein, J.L.
Structure of mycobacterial respiratory complex I.
Proc.Natl.Acad.Sci.USA, 120:e2214949120-e2214949120, 2023

PubMed Abstract: Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the "orphan" two-component response regulator protein MSMEG_2064 as a subunit of the assembly. MSMEG_2064 in the complex occupies a site similar to the proposed redox-sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel, comparable to ubiquinone in other structures and suggesting a conserved quinone binding mechanism.

PubMed: 36952383
DOI: 10.1073/pnas.2214949120

実験手法

ELECTRON MICROSCOPY (2.7 Å)