Structure of Complex I

Complex I is the first enzyme of the respiratory chain and plays a central role in cellular energy production. It has been implicated in many human neurodegenerative diseases, as well as in ageing. One of the biggest membrane protein complexes, varying in size from 0.5 to 1 MDa, it is an L-shaped assembly consisting of hydrophilic and membrane domains. Previously, we determined the structure of the hydrophilic domain in several redox states. It established the pathway for electron transfer from NADH to quinone via seven Fe-S clusters. Recently, we solved the structure of 6 out of 7 membrane domain subunits and described the architecture the entire bacterial complex I. This progress in structural characterization of the enzyme finally allows us to begin to understand the mechanism of this large molecular machine. The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long α-helix, akin to the coupling rod of a steam engine.