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Science  22 Feb 2002:
Vol. 295, Issue 5559, pp. 1427
DOI: 10.1126/science.295.5559.1427c

Maintaining secure boundaries that interdict passage of small molecules is especially challenging because cells need to pump ions across these boundaries in an energetically uphill direction. For a family of enzymes known as the P-type ATPases, exemplified by the sarcoplasmic reticulum (SR) Ca2+-ATPase, the energy is supplied by the hydrolysis of ATP, and ion transport is effected by sequential changes in access and affinity. The ion binding site switches between two states: In E1, it offers a high-affinity calcium binding site to the cytoplasm (where calcium concentrations are low); in E2, the same binding site has low affinity for calcium and is accessible only from the lumen of the SR. This transition is driven by transfer of the high-energy phosphate, first from ATP to an aspartate (E1 to E1-P) and then from the aspartate to water (E2-P to E2).

Xu et al. have fitted the atomic coordinates of the crystal structure of the Ca pump in the E1 state into a 6-angstrom cryoelectronmicroscopy structure of the E2 state. Two of the three cytoplasmic domains (the N- and β-domains) undergo large rotations, which serve to bring the ATP-binding site close to the all-important aspartate. The membrane-proximal P-domain appears to function as a fulcrum, enabling two-way transmission of the rotational changes in the cytoplasmic domains to changes in the angular orientation of the transmembrane helices M4 and M5, which appear to move like an inexpert pair of chopsticks. — GJC

J. Mol. Biol.316, 201 (2002).

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