Efremov, Rouslan G ; Baradaran, Rozbeh ; Sazanov, Leonid AIST Austria
Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. We have determined the structure of its hydrophilic domain previously. Here, we report the α-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 Å resolution. The antiporter-like subunits NuoL/M/N each contain 14 conserved transmembrane (TM) helices. Two of them are discontinuous, as in some transporters. Unexpectedly, subunit NuoL also contains a 110-Å long amphipathic α-helix, spanning almost the entire length of the domain. Furthermore, we have determined the structure of the entire complex I from Thermus thermophilus at 4.5 Å resolution. The L-shaped assembly consists of the α-helical model for the membrane domain, with 63 TM helices, and the known structure of the hydrophilic domain. The architecture of the complex provides strong clues about the coupling mechanism: the conformational changes at the interface of the two main domains may drive the long amphipathic α-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.
This work was funded by the Medical Research Council.
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Efremov R, Baradaran R, Sazanov LA. The architecture of respiratory complex I. Nature. 2010;465(7297):441-445. doi:10.1038/nature09066
Efremov, R., Baradaran, R., & Sazanov, L. A. (2010). The architecture of respiratory complex I. Nature, 465(7297), 441–445. https://doi.org/10.1038/nature09066
Efremov, Rouslan, Rozbeh Baradaran, and Leonid A Sazanov. “The Architecture of Respiratory Complex I.” Nature 465, no. 7297 (2010): 441–45. https://doi.org/10.1038/nature09066.
R. Efremov, R. Baradaran, and L. A. Sazanov, “The architecture of respiratory complex I,” Nature, vol. 465, no. 7297, pp. 441–445, 2010.
Efremov R, Baradaran R, Sazanov LA. 2010. The architecture of respiratory complex I. Nature. 465(7297), 441–445.
Efremov, Rouslan, et al. “The Architecture of Respiratory Complex I.” Nature, vol. 465, no. 7297, Nature Publishing Group, 2010, pp. 441–45, doi:10.1038/nature09066.