Structure of V-ATPase from the mammalian brain

Author:

Abbas Yazan M.1ORCID,Wu Di2,Bueler Stephanie A.1,Robinson Carol V.2ORCID,Rubinstein John L.134ORCID

Affiliation:

1. Molecular Medicine Program, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.

2. Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford OX1 3QZ, UK.

3. Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

4. Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.

Abstract

Snapshots of a rotary pump Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-hydrolysis–driven proton pumps. In neurons, V-ATPase activity generates a proton gradient across the membrane of synaptic vesicles so that neurotransmitters can be loaded into the vesicles. Abbas et al. developed a method to purify V-ATPase from rat brain and determined the structure of the entire complex by cryo–electron microscopy. Native mass spectrometry showed that the preparation was homogeneous and complemented structural studies by confirming the subunit composition. Three rotational states were resolved at better than 4-angstrom resolution, providing insight into the conformational changes that couple ATP hydrolysis to proton pumping. Science , this issue p. 1240

Funder

Wellcome

Canadian Institutes of Health Research

European Research Council

Canada Research Chairs

The Hospital For Sick Children

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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