Baradaran, Rozbeh ; Berrisford, John M ; Minhas, Gurdeep S ; Sazanov, Leonid AIST Austria
Complex I is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of NADH:ubiquinone electron transfer to proton translocation. It is also implicated in many common human neurodegenerative diseases. Here, we report the first crystal structure of the entire, intact complex I (from Thermus thermophilus) at 3.3 Å resolution. The structure of the 536-kDa complex comprises 16 different subunits, with a total of 64 transmembrane helices and 9 iron-sulphur clusters. The core fold of subunit Nqo8 (ND1 in humans) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, which completes the fourth proton-translocation pathway (present in addition to the channels in three antiporter-like subunits). The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near iron-sulphur cluster N2. Notably, the chamber is linked to the fourth channel by a 'funnel' of charged residues. The link continues over the entire membrane domain as a flexible central axis of charged and polar residues, and probably has a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone-reaction chamber enables the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle.
This work was funded by the Medical Research Council.
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Baradaran R, Berrisford J, Minhas G, Sazanov LA. Crystal structure of the entire respiratory complex i. Nature. 2013;494(7438):443-448. doi:10.1038/nature11871
Baradaran, R., Berrisford, J., Minhas, G., & Sazanov, L. A. (2013). Crystal structure of the entire respiratory complex i. Nature, 494(7438), 443–448. https://doi.org/10.1038/nature11871
Baradaran, Rozbeh, John Berrisford, Gurdeep Minhas, and Leonid A Sazanov. “Crystal Structure of the Entire Respiratory Complex I.” Nature 494, no. 7438 (2013): 443–48. https://doi.org/10.1038/nature11871.
R. Baradaran, J. Berrisford, G. Minhas, and L. A. Sazanov, “Crystal structure of the entire respiratory complex i,” Nature, vol. 494, no. 7438, pp. 443–448, 2013.
Baradaran R, Berrisford J, Minhas G, Sazanov LA. 2013. Crystal structure of the entire respiratory complex i. Nature. 494(7438), 443–448.
Baradaran, Rozbeh, et al. “Crystal Structure of the Entire Respiratory Complex I.” Nature, vol. 494, no. 7438, Nature Publishing Group, 2013, pp. 443–48, doi:10.1038/nature11871.