Toward a characterization of the connecting module of complex I

Complex I [NADH-ubiquinone oxidoreductase (complex 1, EC 1.6.5.3)] couples electron transfer between NADH and ubiquinone to proton transport across th e bacterial cytoplasmic membrane and the mitochondrial inner membrane. This sophisticated enzyme consists of three specialized modules: (1) a hydrophi lic NADH-oxidizing module that constitutes the input machinery of the enzym e; (2) a hydrophobic module that anchors the enzyme in the membrane and mus t take part in proton transport; and (3) a connecting domain that links the two previous modules. Using the complex I of Rhodobacter capsulatus, we de veloped a genetic study of the structure and function of the connecting mod ule. In the present review, we put together the salient results of these st udies, with recent reports of the literature, to try and elucidate the stru cture of the connecting module and its potential role in the coupling proce ss between electron. and proton flux within complex 1. From this overview, we conclude that the NUOB-NUOD dimer of the connecting module and a hydroph obic subunit such as NUOH must share a quinone-reduction site. The function of this site in the mechanism of complex I is discussed.