Structural Basis for Redox-Linked Proton Translocation by Mitochondrial Complex I

Proton-pumping NADH-dehydrogenase (complex I) is the largest and most complicated enzyme of the respiratory chain. Complex I from the aerobic yeast Yarrowia lipolytica comprises 14 central subunits that harbor the bioenergetic core functions and 28 accessory subunits; the total mass is 963.7 kDa. We have crystallized the enzyme complex for structure determination by X-ray crystallography. Our structural model showed that iron-sulfur cluster N2 implicated in ubiquinone reduction resides at a remarkable distance from the membrane surface. The membrane arm comprises more than 70 transmembrane segments that can be assigned to two distinct subdomains. The arrangement of functional modules indicates that redox-linked proton translocation is governed by a conformational coupling mechanism.