7B0N
A 3.7-angstrom structure of Yarrowia lipolytica complex I with an R121M mutation in NUCM.
This is a non-PDB format compatible entry.
Summary for 7B0N
| Entry DOI | 10.2210/pdb7b0n/pdb |
| EMDB information | 11969 |
| Descriptor | NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 6, NADH-ubiquinone oxidoreductase chain 4L, ... (52 entities in total) |
| Functional Keywords | nadh:ubiquinone oxidoreductase, complex i, membrane protein |
| Biological source | Yarrowia lipolytica More |
| Total number of polymer chains | 42 |
| Total formula weight | 990186.76 |
| Authors | |
| Primary citation | Hameedi, M.A.,Grba, D.N.,Richardson, K.H.,Jones, A.J.Y.,Song, W.,Roessler, M.M.,Wright, J.J.,Hirst, J. A conserved arginine residue is critical for stabilizing the N2 FeS cluster in mitochondrial complex I. J.Biol.Chem., 296:100474-100474, 2021 Cited by PubMed Abstract: Respiratory complex I (NADH:ubiquinone oxidoreductase), the first enzyme of the electron-transport chain, captures the free energy released by NADH oxidation and ubiquinone reduction to translocate protons across an energy-transducing membrane and drive ATP synthesis during oxidative phosphorylation. The cofactor that transfers the electrons directly to ubiquinone is an iron-sulfur cluster (N2) located in the NDUFS2/NUCM subunit. A nearby arginine residue (R121), which forms part of the second coordination sphere of the N2 cluster, is known to be posttranslationally dimethylated but its functional and structural significance are not known. Here, we show that mutations of this arginine residue (R121M/K) abolish the quinone-reductase activity, concomitant with disappearance of the N2 signature from the electron paramagnetic resonance (EPR) spectrum. Analysis of the cryo-EM structure of NDUFS2-R121M complex I at 3.7 Å resolution identified the absence of the cubane N2 cluster as the cause of the dysfunction, within an otherwise intact enzyme. The mutation further induced localized disorder in nearby elements of the quinone-binding site, consistent with the close connections between the cluster and substrate-binding regions. Our results demonstrate that R121 is required for the formation and/or stability of the N2 cluster and highlight the importance of structural analyses for mechanistic interpretation of biochemical and spectroscopic data on complex I variants. PubMed: 33640456DOI: 10.1016/j.jbc.2021.100474 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.7 Å) |
Structure validation
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