Structure of the hexameric fungal plasma membrane proton pump in its autoinhibited state.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34757782.
- Also identified by DOI 10.1126/sciadv.abj5255 and PMC identifier 8580308.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The fungal plasma membrane H<sup>+</sup>-ATPase Pma1 is a vital enzyme, generating a proton-motive force that drives the import of essential nutrients. Autoinhibited Pma1 hexamers in the plasma membrane of starving fungi are activated by glucose signaling and subsequent phosphorylation of the autoinhibitory domain. As related P-type adenosine triphosphatases (ATPases) are not known to oligomerize, the physiological relevance of Pma1 hexamers remained unknown. We have determined the structure of hexameric Pma1 from <i>Neurospora crassa</i> by electron cryo-microscopy at 3.3-Å resolution, elucidating the molecular basis for hexamer formation and autoinhibition 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.