Mechanistic analysis of catalysis and regulation of the fungal proton pump Pma1

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A lipid membrane separates the 'inside' from the 'outside' of each cell in all living organisms. In order to exchange material and information with its surroundings, every cell possesses various transport proteins embedded in its outer membrane. These proteins control what can enter and exit cells, and they are very important gate-keepers between the 'inside' and 'outside' worlds.One large family of such membrane transport proteins literally 'pump' ions across the membrane, thereby building up important imbalances, which are then fuelling other processes, such as nutrient uptake, nerve excitation, or muscle contraction. One such pump, called Pma1, generates a fundamentally important proton gradient in the membranes of all fungi. As a molecular machine that specifically pumps the smallest of all ions - single protons - across the membrane, it is not only interesting in itself, but it is also important from an economic point of view: Pma1 does not exist in humans or animals, and plants have a related but different proton pump. Since fungi cannot survive without Pma1, it could be the target of novel fungicides with a low risk of harmful effects on animals, humans or plants. Such new targets are urgently needed in light of emerging resistances of harmful fungi against those fungicides which are currently in extensive use to protect plants and crops from fungal pests.This research project will reveal how Pma1 transports protons across membranes, by combining state-of-the-art biochemical and biophysical methods to make the molecule itself visible to the human eye. The project will lead to a deeper understanding of the actual proton pumping process, and it will provide the information necessary to develop new fungicides.