Rubinstein Lab’s Nature Image
V-ATPases are proton pumps that control the pH in many compartments within cells. V-ATPase activity is critical for the immune system (where acidic compartments in cells are used to destroy invading bacteria), cell growth (where compartments with different pHs are needed for molecules to be built and destroyed), the transmission of signals in the brain (where V-ATPases are needed to load packets of neurotransmitters that are deposited between neurons), and in bone maintenance (where V-ATPases help take up bone mineral so that fresh minerals can be deposited). Aberrant V-ATPase activity also helps tumors to invade surrounding tissues. Despite this importance, the mechanism by which V-ATPases pump protons remains mysterious.
The Rubinstein Lab has employed state-of-the-art electron microscopy techniques with novel computational algorithms and a new type of electron-detecting camera to calculate the highest-resolution structures ever determined for a V-ATPase. They have also been able to image this macromolecular machine in different states so that we can see how it moves in order to couple the use of ATP to proton pumping. This understanding of V-ATPase structure and function will allow for understanding the various processes the V-ATPase controls and enable design of drugs that influence its activity.
