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Figure 4.
Figure 4: Mechanism of proton transport by plasma membrane
H^+-ATPase. E2-model forms of the H^+-ATPase were made by
structural alignment of our E1-AMPPCP structure with the E2P
structure of the Ca^2+-ATPase^26 and the E2-P* structure (E2
occluded state of the pump) of the Ca^2+-ATPase (PDB code 1XP5).
Asp 684 is the central proton donor/acceptor of the pump, and
together with Arg 655 it lines a centrally located water-filled
cavity. In the E1 conformation, hydrogen bonding between Asp 684
and Asn 106 gives preference to the protonated form of Asp 684
(E1-ATP structure). Conformational movements in the membrane
region, coupled to E1–E2 transitions, result in opening of the
cavity towards the proton exit pathway (E2P model) and interrupt
hydrogen bonding between Asn 106 and Asp 684; this results in
proton release from Asp 684, now exposed to the extracellular
environment. Placement of Arg 655 towards Asp 684 at the exit
channel also stimulates proton release from Asp 684, and
provides a positively charged plug in this area of the molecule
that prevents extracellular protons from re-protonating Asp
684. At the same time Arg 655 functions as a built-in
counter-ion that neutralizes the negative charge on Asp 684 and
promotes swift formation of the occluded E2-P* transition state
(E2P* model), dephosphorylation and transition to the E2 form.
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