|Title||The architecture of respiratory complex I.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Efremov, R. G., R. Baradaran, and L. A. Sazanov|
|Date Published||2010 May 27|
|Keywords||Benzoquinones, Binding Sites, Cell Membrane, Crystallography, X-Ray, Electron Transport Complex I, Escherichia coli, Models, Molecular, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Subunits, Structure-Activity Relationship, Thermus thermophilus|
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 alpha-helical structure of the membrane domain of complex I from Escherichia coli at 3.9 A 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-A long amphipathic alpha-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 A resolution. The L-shaped assembly consists of the alpha-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 alpha-helix of NuoL in a piston-like motion, tilting nearby discontinuous TM helices, resulting in proton translocation.
|Grant List||/ / Medical Research Council / United Kingdom|
The architecture of respiratory complex I.