General and specific interactions of the phospholipid bilayer with P-type ATPases

05 September 2019

Protein structure and function are modulated via interactions with their environment, representing both the surrounding aqueous media and lipid membranes that have an active role in shaping the structural topology of membrane proteins. Compared to a decade ago, there is now an abundance of crystal structural data on membrane proteins, which together with their functional studies have enhanced our understanding of the salient features of lipid-protein interactions. It is now important to recognize that membrane proteins are regulated by both: (1) general lipid-protein interactions, where the general physicochemical properties of the lipid environment affect the conformational flexibility of a membrane protein; and (2) by specific lipid-protein interactions, where lipid molecules directly interact via chemical interactions with specific lipid-binding sites located on the protein. However, due to local differences in membrane composition, thickness and lipid packing, local membrane physical properties and hence the associated lipid-protein interactions also differ due to membrane location, even for the same protein. Such a phenomenon has been shown to be true for one family of integral membrane ion pumps, the P2-type adenosine triphosphatases (ATPases). Despite being highly homologous, individual members of this family have distinct structural and functional activity and are an excellent candidate to highlight how the local membrane physical properties and specific lipid-protein interactions play a vital role in facilitating the structural rearrangements of these proteins necessary for their activity. Hence in this review, we focus on both the general and specific lipid-protein interactions and will mostly discuss the structure-function relationships of the following P2-type ATPases, Na+,K+-ATPase (NKA), gastric H+,K+-ATPase (HKA) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), in concurrence with their lipid environment.