Volume 232, 2021

Order-disorder transitions of cytoplasmic N-termini in the mechanisms of P-type ATPases

Abstract

Membrane protein structure and function are modulated via interactions with their lipid environment. This is particularly true for integral membrane pumps, the P-type ATPases. These ATPases play vital roles in cell physiology, where they are associated with the transport of cations and lipids, thereby generating and maintaining crucial (electro-)chemical potential gradients across the membrane. Several pumps (Na+, K+-ATPase, H+, K+-ATPase and the plasma membrane Ca2+-ATPase) which are located in the asymmetric animal plasma membrane have been found to possess polybasic (lysine-rich) domains on their cytoplasmic surfaces, which are thought to act as phosphatidylserine (PS) binding domains. In contrast, the sarcoplasmic reticulum Ca2+-ATPase, located within an intracellular organelle membrane, does not possess such a domain. Here we focus on the lysine-rich N-termini of the plasma-membrane-bound Na+, K+- and H+, K+-ATPases. Synthetic peptides corresponding to the N-termini of these proteins were found, via quartz crystal microbalance and circular dichroism measurements, to interact via an electrostatic interaction with PS-containing membranes, thereby undergoing an increase in helical or other secondary structure content. As well as influencing ion pumping activity, it is proposed that this interaction could provide a mechanism for sensing the lipid asymmetry of the plasma membrane, which changes drastically when a cell undergoes apoptosis, i.e. programmed cell death. Thus, polybasic regions of plasma membrane-bound ion pumps could potentially perform the function of a “death sensor”, signalling to a cell to reduce pumping activity and save energy.

Graphical abstract: Order-disorder transitions of cytoplasmic N-termini in the mechanisms of P-type ATPases

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
16 अप्रैल 2020
Accepted
01 सितम्बर 2020
First published
01 सितम्बर 2020

Faraday Discuss., 2021,232, 172-187

Order-disorder transitions of cytoplasmic N-termini in the mechanisms of P-type ATPases

K. R. Hossain, D. Clayton, S. C. Goodchild, A. Rodger, R. J. Payne, F. Cornelius and R. J. Clarke, Faraday Discuss., 2021, 232, 172 DOI: 10.1039/D0FD00040J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements