Evolutionary Perspective on the Coupling Mechanism of Complex I and Related Enzymes

Abstract

Complex I is an energy transducing enzyme present in the three domains of life. This enzyme catalyzes the oxidation of NADH and the reduction of quinone coupled to charge translocation across the membrane. In this way, it contributes to the establishment of the transmembrane difference of electrochemical potential which is used for ATP synthesis, solute transport and motility. The research on this enzyme has gained a new enthusiasm, especially after the resolution of the crystallographic structures of bacterial and mitochondrial complexes. Most attention is now dedicated to the investigation of the energy coupling mechanism. In this work, we made a thorough investigation of complex I and group 4 [NiFe] hydrogenases and established a third member of this family of proteins: the energy-converting hydrogenase related complex. We observed that four subunits (NuoB, D, H and antiporter-like) are common to the 3 types of complexes and we have denominated these subunits as the universal adaptor. We further explored the properties of the adaptor by investigating the structural characteristics of the antiporter-like subunit. We observed that the adaptor contains an antiporter-like subunit with a long amphipathic α-helix. The long helix is a common denominator that has been conserved through evolution. This should reflect a key role of such helix in the coupling mechanism of this family of enzymes. We are currently investigating the structural motifs involved in Na+/H+ antiporter activity in complex I and related complexes. These findings are a step forward in the investigation of the coupling mechanism of complex I.