Figure 5. The antiport mechanism of the Mrp complex and its conservation in complex I and MBH.

(a) A likely state of the Mrp complex in the current structure, as a part of the catalytic cycle. Key glutamates from the central axis are shown as red circles and key lysines as blue circles, with charged state depicted by filled circle and neutral state by empty circle. Key helices where these residues sit are numbered and shown as broken where applicable. Coupling points are indicated by red dashed ovals. Electrostatic interactions are indicated as thick dashed lines. Possible lateral re-distribution of protons between MrpA and MrpD is indicated as alternative to the direct entry of protons to MrpD from the periplasm. Na⁺ ion (blue) is bound in the coupling point and the large Na⁺ cavity mid-pathway is indicated as an empty oval. A sequence of events leading up to this state is described in the text. (b) An alternative state of the Mrp complex as another part of the catalytic cycle. Na⁺ ion is expelled into the periplasm and coupling points become neutral. (c) Complex I contains one additional MrpD-like subunit (orange, Nqo13/NuoM), with the change of LysTMH12 to glutamate. The coupling points between the APLS are conserved and the coupling point with Na⁺ is replaced by coupling to the charge of glutamates in the E-channel. (d) MBH instead of a MrpA-like subunit contains a [NiFe] hydrogenase module, which oxidises ferredoxin and reduces protons to hydrogen. This module has a chain of glutamates similarly to complex I and their charge likely boosts proton translocation into the cell (opposite direction to complex I) via the modified coupling point (red dashed oval on the left). The H⁺/Na⁺ coupling point and mechanism are retained from the Mrp.