Structure, function and biogenesis of the fungal proton pump Pma1

Abstract

The fungal plasma membrane proton pump Pma1 is an integral plasma membrane protein of the P-type ATPase family. It is an essential enzyme responsible for maintaining a constant cytosolic pH and for energising the plasma membrane to secondary transport processes. Due to its importance for fungal survival and absence from animals, Pma1 is also a highly sought-after drug target. Until recently, its characterisation has been limited to functional, mutational and localisation studies, due to a lack of high-resolution structural information. The determination of three cryo-EM structures of Pma1 in its unique hexameric state offers a new level of understanding the molecular mechanisms underlying the protein's stability, regulated activity and druggability. In light of this context, this article aims to review what we currently know about the structure, function and biogenesis of fungal Pma1.

Keywords: Auto-inhibition; Mutational data; Plasma membrane proton ATPase; Proton pump; Structure-function relationship.