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 اپریل 2020
Accepted
01 ستمبر 2020
First published
01 ستمبر 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

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