Key result
Physiological ATP eliminates SERCA up-down motion, indicating a catalytic pathway distinct from the Albers-Post scheme.
Why the study?
Static crystal structures of ion pumps provide limited insight into real-time conformational changes during ion transport, necessitating dynamic visualization of SERCA activity.
Real-time visualization of SERCA reveals that under physiological conditions, its catalytic pathway differs from the traditional Albers-Post scheme.
Real-time SERCA imaging now feasible; extends static structures but leaves open cardiac therapeutic relevance.
Studies of ion pumps, such as ATP synthetase and Ca(2+)-ATPase, have a long history. The crystal structures of several kinds of ion pump have been resolved, and provide static pictures of mechanisms of ion transport. In this study, using fast-scanning atomic force microscopy, we have visualized conformational changes in the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in real time at the single-molecule level. The analyses of individual SERCA molecules in the presence of both ATP and free Ca(2+) revealed up-down structural changes corresponding to the Albers-Post scheme. This fluctuation was strongly affected by the ATP and Ca(2+) concentrations, and was prevented by an inhibitor, thapsigargin. Interestingly, at a physiological ATP concentrations, the up-down motion disappeared completely. These results indicate that SERCA does not transit through the shortest structure, and has a catalytic pathway different from the ordinary Albers-Post scheme under physiological conditions.
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Yokokawa et al. (2011) studied this question. ATP and free Ca(2+) was evaluated on Conformational changes in SERCA molecules. Single-molecule analysis revealed that at physiological ATP concentrations, the up-down motion of SERCA disappears, indicating a catalytic pathway different from the ordinary Albers-Post scheme.
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