Key result
Protonation of the transmembrane transport sites controls the hierarchical organization and amplitude of preexisting rigid-body domain motions to shift the equilibrium between E1 and E2 states.
Ligand-induced modulation of preexisting domain motions is likely a common mechanism driving structural transitions in the P-type ATPase superfamily.
ion rapidly (<10 ns) binds to the transmembrane transport sites and induces a kink in M5, disrupts the M3-M5 interface, and increases the mobility of the M3/A-M3 linker. Principal component analysis showed that counter-rotation of the cytosolic N-A domains about the membrane normal axis, which is the primary motion driving the E2-to-E1 transition, is present in both protonated and deprotonated E2 states; however, protonation-dependent structural changes in the transmembrane domain control the hierarchical organization and amplitude of this motion. We propose that preexisting rigid-body domain motions underlie structural transitions of SERCA, where the functionally important directionality is preserved while transport site protonation controls the dominance and amplitude of motion to shift the equilibrium between the E1 and E2 states. We conclude that ligand-induced modulation of preexisting domain motions is likely a common theme in structural transitions of the P-type ATPase superfamily.
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Gortari et al. (2017) studied this question. Protonation vs. Deprotonated state was evaluated on Structural transitions and domain motions of SERCA. Protonation of the transmembrane transport sites controls the hierarchical organization and amplitude of preexisting rigid-body domain motions to shift the equilibrium between E1 and E2 states.
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