Identifying the proton loading site cluster in the ba cytochrome c oxidase that loads and traps protons

Abstract

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Protein Motifs for Proton Transfers That Build the Transmembrane Proton Gradient

“…In the crystal structures and in protein equilibrated in MD trajectories without the water cavity FIGURE 10 | Complex PLS on the P-side of the B-type CcO. The proton moves between Prop A [trapped unloaded (tU), with very low proton affinity] to D372 [dynamic unloaded (dU)] where electron transfer to Heme A 3 or CuB in the BNC active site 15 Å distant will lead to proton loading into the cluster (Cai et al, 2020). In the loaded state one proton is on D372.…”

“…The BNC is reduced stepwise, one at a time to store four electrons. O 2 reduction takes place in one step in the fully reduced BNC ( Kaila et al, 2010 ; Cai et al, 2020 ). O 2 production likewise takes place in one step in the fully oxidized OEC of PSII.…”

“…The P-side of all CcOs has a tangled cluster of strongly interacting polar and protonatable residues that do not provide an obvious single exit path, although linear paths have been suggested ( Popović and Stuchebrukhov, 2005 ; Björck et al, 2019 ). The hydrogen bond network on the P-side of A- and B-type CcO, was analyzed using Monte Carlo sampling and network analysis ( Cai et al, 2018 ; Cai et al, 2020 ). Calculations were initiated with experimental crystal structures as well as with snapshots from MD trajectories carried out in different redox states of the hemes and protonation states of key residues.…”

“…On the P-side of the B-type CcO, an extended cluster of six residues was found to behave as a PLS ( Figure 10 ) ( Cai et al, 2020 ). The unloaded PLS has one proton bound (net charge -4) while the loaded cluster has two protons.…”

“…However, representative structures will be shown to reveal interior regions with tangled webs of polar and protonatable groups and many water molecules ( Krammer et al, 2009 ; Cai et al, 2020 ; Khaniya et al, 2020 ). These complex proton transfer paths provide multiple choices for protons to follow.…”