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

Abstract

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 P2type ATPases, Na + ,K + -ATPase (NKA), gastric H + ,K + -ATPase (HKA), and sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA), in concurrence with their lipid environment.

Deciphering ion transport and ATPase coupling in the intersubunit tunnel of KdpFABC

“…of CL probably reflects the effect on the rate-limiting step. Similar lipid-mediated effects have been shown for other P-type ATPases 25,26 .…”

Mechanical stress triggers nuclear remodeling and the formation of transmembrane actin nuclear lines with associated nuclear pore complexes

“…In addition, NE proteins that are not known to be part of a NE–cytoskeletal interaction, such as SERCA2 (Sarco(endo)plasmic reticulum Ca 2+ -ATPase) ( Hossain and Clarke 2019 ) or Sec61B (Rapoport 2007), do not accumulate in robust nuclear lines in response to uniaxial cyclic stretch, as compared with SUN2 or other nuclear line constituents described in this paper. Immunolocalization and microscopy in the xyz dimensions were consistent with endoplasmic reticulum and NE distributions of SERCA2 (Supplemental Figure S5, A–C; Supplemental Videos S4–S7) and Sec61B (Supplemental Figure S5, D–F; Supplemental Videos S8–S11) in stretch-stimulated cells, with minimal nuclear line signals along actin SFs.…”

Protein Adsorption on Solid Supported Membranes: Monitoring the Transport Activity of P-Type ATPases

“…However, also for the well-characterized P2-type ATPases Na + ,K + -ATPase, and SERCA, a complexity of regulatory mechanisms has emerged [ 4 , 19 ], which requires further detailed investigation. We think that the SSM method can be usefully employed to characterize the interaction of P-type ATPases with specific regulatory partners, which can be small molecules, soluble proteins, transmembrane peptides, or the surrounding lipid bilayer [ 110 ].…”