Truncation of subunit ND2 disrupts the threefold symmetry of the antiporter‐like subunits in complex I from higher metazoans

Three of the conserved, membrane-bound subunits in NADH:ubiquinone oxidoreductase (complex I) are related to one another, and to Mrp sodium-proton antiporters. Recent structural analysis of two prokaryotic complexes I revealed that the three subunits each contain fourteen transmembrane helices that overlay in structural alignments: the translocation of three protons may be coordinated by a lateral helix connecting them together (Efremov, R.G., Baradaran, R. and Sazanov, L.A. (2010). The architecture of respiratory complex I. Nature 465, 441-447). Here, we show that in higher metazoans the threefold symmetry is broken by the loss of three helices from subunit ND2; possible implications for the mechanism of proton translocation are discussed.