title: The 'antiporter module' of respiratory chain complex I includes the MrpC/NuoK subunit -- a revision of the modular evolution scheme.
abstract: Respiratory chain Complex I or NADH:quinone oxidoreductase catalyzes oxidation of NADH in the mitochondrial matrix or bacterial cytoplasm and reduction of quinone in the membrane, coupled to pumping of 4H(+)/2e(-) across the membrane. The same enzyme complex is also capable of the reverse reaction, i.e. Deltamu(H(+))-supported NAD(+) reduction. The molecular mechanism that couples electron transfer to proton pumping is not understood. The Complex I enzyme, containing 14 protein subunits necessary for function, has evolved from smaller functional building blocks. Three Complex I protein subunits, NuoL, NuoM and NuoN, show primary sequence similarity to one particular class of antiporters, and are thus predicted to play a role in the proton translocation machinery. These antiporters, MrpA and MrpD are encoded by a conserved gene cluster, that contains seven genes. In previous work we have determined that these antiporters come in two subclasses, MrpA-type and MrpD-type, and that the Complex I subunit NuoL is more closely related to MrpA and NuoM and N are more closely related to the MrpD antiporter. This implied that both MrpA and MrpD had been recruited to Complex I, rather than arising from gene duplications of one antiporter encoding gene. In this work we show that MrpC and NuoK are homologous proteins. The most plausible explanation for these findings is that a multisubunit antiporter complex was recruited to the ancestral enzyme. We further conclude that the last common ancestor of the Complex I enzyme family and membrane bound NiFe hydrogenases of type 3 and 4 contained the NuoKLMN subunit module.
authors.affiliation: Department of Biochemistry, Lund University, PO Box 124, 22100 Lund, Sweden.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Mathiesen
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hägerhäll
mesh_terms: D000595:Amino Acid Sequence; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics; D042967:Electron Transport Complex I / Q000737:chemistry* / Q000235:genetics; D019143:Evolution, Molecular; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D005810:Multigene Family; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D017494:Proton Pumps / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D017920:Antiporters; D021122:Protein Subunits; D017494:Proton Pumps; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I