Structure of the hexameric fungal plasma membrane proton pump in its auto-inhibited state

Heit, S.; Geurts, M. M. G.; Murphy, B. J.; Corey, R. A.; Mills, D. J.; Kühlbrandt, W.; Bublitz, M.

doi:10.1101/2021.04.30.442159

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bioRxiv · 10.1101/2021.04.30.442159

Structure of the hexameric fungal plasma membrane proton pump in its auto-inhibited state

Heit, S.·Geurts, M. M. G.·Murphy, B. J.·Corey, R. A.·Mills, D. J.·Kühlbrandt, W.·Bublitz, M.

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Abstract

The fungal plasma membrane H+-ATPase Pma1 is a vital enzyme, generating a proton-motive force that drives the import of essential nutrients. Auto-inhibited Pma1 hexamers in starving fungi are activated by glucose signalling resulting in phosphorylation of the auto-inhibitory domain. As related P-type ATPases are not known to oligomerise, the physiological relevance of Pma1 hexamers remains unknown. We have determined the structure of hexameric Pma1 from Neurospora crassa by cryo-EM at 3.3 [A] resolution, elucidating the molecular basis for hexamer formation and auto-inhibition, and providing a basis for structure-based drug development. Coarse-grained molecular dynamics simulations in a lipid bilayer suggest lipid-mediated contacts between monomers and a substantial protein-induced membrane deformation that could act as a proton-attracting funnel.

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Heit, S., Geurts, M. M. G., Murphy, B. J., Corey, R. A., Mills, D. J., Kühlbrandt, W., Bublitz, M.. 2021-04-30. Structure of the hexameric fungal plasma membrane proton pump in its auto-inhibited state. https://doi.org/10.1101/2021.04.30.442159

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