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Structure Of The Plasma Membrane Proton Pump Offers A First Glimpse Of The Mechanism Of Ion Pumping Across Membranes

April 27, 1998

A research team from the Max Planck Institute of Biophysics in Frankfurt/Germany, and the University of North Carolina, Chapel Hill/NC, has determined the structure of the plasma membrane proton ATPase at a resolution of about 0.8 nm by electron cryomicroscopy of two-dimensional crystals (Nature, vol. 392, 23 April 1998, 840).

The proton ATPase is a membrane protein which uses energy derived from ATP hydrolisis to pump protons out of the cell, there by controlling its internal pH. Similar proteins control the heart rhythm, the action potential of nerve cells, and muscle contraction. All these ion pumps work in the same way as the proton ATPase and are likely to have similar structures.

Manfred Auer and Werner Kühlbrandt of the Department of Structural Biology at the Max Planck Insitute of Biophysics developed a new method to grow two-dimensional crystals on a carbon support film and used these for structure determination by electron cryo-microscopy, at a resolution of 0.8 nm. Gene A. Scarborough, from the Department of Pharmacology at the University of North Carolina, provided the protein of which he was able to grow three-dimensional crystals, thus providing the essential starting point for the 2D crystallization experiments.

The structure of the closely related calcium ATPase, also determined by electron microscopy at comparable resolution, is reported in the same issue of nature (Zhang et al, nature, vol. 392, 23 April 1998, 835). Interestingly, the two structures are similar in the transmembrane domain, but they appear to differ significantly in the large cytoplasmic region. Presumably, the differences in the two structures represent the conformational change that occurs upon ion binding. Such ligand induced conformational changes are almost certainly intimately involved in the ion occlusion and molecular mechanisms of ion translocation catalyzed by this important family of ion pumps.


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