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

    Year: 2021

    Journal: Faraday Discuss., Volume 232, DEC 24, page 172–187

    Authors: Hossain, Khondker R.; Clayton, Daniel; Goodchild, Sophia C.; Rodger, Alison; Payne, Richard J.; Cornelius, Flemming; Clarke, Ronald J.

    Organizations: Australian Research Council [DP121003548, DP150101112, DP170101732]; Danish Medical Research Council; Novo Nordisk Foundation

    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.
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