Efremov, Rouslan G; Sazanov, Leonid AIST Austria
Complex I is the first and largest enzyme of the respiratory chain, coupling electron transfer between NADH and ubiquinone to the translocation of four protons across the membrane. It has a central role in cellular energy production and has been implicated in many human neurodegenerative diseases. The L-shaped enzyme consists of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain. Here we report the crystal structure of the Esherichia coli complex I membrane domain at 3.0 Ã. resolution. It includes six subunits, NuoL, NuoM, NuoN, NuoA, NuoJ and NuoK, with 55 transmembrane helices. The fold of the homologous antiporter-like subunits L, M and N is novel, with two inverted structural repeats of five transmembrane helices arranged, unusually, face-to-back. Each repeat includes a discontinuous transmembrane helix and forms half of a channel across the membrane. A network of conserved polar residues connects the two half-channels, completing the proton translocation pathway. Unexpectedly, lysines rather than carboxylate residues act as the main elements of the proton pump in these subunits. The fourth probable proton-translocation channel is at the interface of subunits N, K, J and A. The structure indicates that proton translocation in complex I, uniquely, involves coordinated conformational changes in six symmetrical structural elements.
This work was funded by the Medical Research Council.
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Efremov R, Sazanov LA. Structure of the membrane domain of respiratory complex i. Nature. 2011;476(7361):414-421. doi:10.1038/nature10330
Efremov, R., & Sazanov, L. A. (2011). Structure of the membrane domain of respiratory complex i. Nature. Nature Publishing Group. https://doi.org/10.1038/nature10330
Efremov, Rouslan, and Leonid A Sazanov. “Structure of the Membrane Domain of Respiratory Complex I.” Nature. Nature Publishing Group, 2011. https://doi.org/10.1038/nature10330.
R. Efremov and L. A. Sazanov, “Structure of the membrane domain of respiratory complex i,” Nature, vol. 476, no. 7361. Nature Publishing Group, pp. 414–421, 2011.
Efremov R, Sazanov LA. 2011. Structure of the membrane domain of respiratory complex i. Nature. 476(7361), 414–421.
Efremov, Rouslan, and Leonid A. Sazanov. “Structure of the Membrane Domain of Respiratory Complex I.” Nature, vol. 476, no. 7361, Nature Publishing Group, 2011, pp. 414–21, doi:10.1038/nature10330.