8E9H

Mycobacterial respiratory complex I, fully-inserted quinone

Summary for 8E9H

• Entry DOI: 10.2210/pdb8e9h/pdb
• EMDB information: 27964
• Descriptor: Two-component system response regulator, NADH-quinone oxidoreductase subunit H, NADH-quinone oxidoreductase subunit J, ... (22 entities in total)
• Functional Keywords: complex, oxidative phosphorylation, nadh-quinone oxidoreductase, iron-sulfur protein, membrane protein
• Biological source: Mycolicibacterium smegmatis MC2 155; More
• Total number of polymer chains: 15
• Total formula weight: 563687.42

Authors

Liang, Y.,Rubinstein, J.L. (deposition date: 2022-08-26, release date: 2022-10-12, Last modification date: 2023-04-05)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.7 Å)