Key result
The Glu309Gln mutant of SERCA1a exhibits large structural rearrangements in both cytoplasmic and transmembrane domains, helping to postulate a mechanism for the E2 to E1 transition.
Why the study?
In the E2 state of SERCA1a, acidic Ca2+-coordinating residues are thought to be protonated, meaning a Glu309Gln substitution was not expected to significantly perturb the structure.
Crystal structures of SERCA1a mutants reveal large structural rearrangements that help explain the mechanism of the E2 to E1 transition triggered by deprotonation of Glu309.
Ca 2+ -ATPase of sarcoplasmic reticulum (SERCA1a) pumps two Ca 2+ per ATP hydrolyzed from the cytoplasm and two or three protons in the opposite direction. In the E2 state, after transferring Ca 2+ into the lumen of sarcoplasmic reticulum, all of the acidic residues that coordinate Ca 2+ are thought to be protonated, including the gating residue Glu309. Therefore a Glu309Gln substitution is not expected to significantly perturb the structure. Here we report crystal structures of the Glu309Gln and Glu309Ala mutants of SERCA1a under E2 conditions. The Glu309Gln mutant exhibits, unexpectedly, large structural rearrangements in both the cytoplasmic and transmembrane domains, apparently uncoupling them. However, the structure definitely represents E2 and, together with the help of quantum chemical calculations, allows us to postulate a mechanism for the E2 → E1 transition triggered by deprotonation of Glu309.
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Tsunekawa et al. (2018) studied this question. Glu309Gln and Glu309Ala mutations in SERCA1a was evaluated on Crystal structures and structural rearrangements. The Glu309Gln mutant of SERCA1a exhibits large structural rearrangements in both cytoplasmic and transmembrane domains, helping to postulate a mechanism for the E2 to E1 transition.
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