Assessing the interaction between the N-terminal region of the membrane protein magnesium transporter A and a lipid bilayer.

This study investigates the interaction of KEIF, the intrinsically disordered N-terminal region of the magnesium transporter MgtA, with lipid bilayers mimicking cell membranes. Combining experimental techniques such as neutron reflectometry (NR), quartz-crystal microbalance with dissipation monitoring (QCM-D), synchrotron radiation circular dichroism (SRCD), and oriented circular dichroism (OCD), with molecular dynamics (MD) simulations, we characterized KEIF's adsorption behavior.
Hypothesis: KEIF undergoes conformational changes upon interacting with lipid bilayers, potentially influencing MgtA's function within the plasma membrane.
Experiments: The study assessed KEIF's structural transitions and position within lipid bilayers under various conditions, including zwitterionic versus anionic bilayers and different salt concentrations. The techniques analyzed adsorption-induced structural shifts and peptide localization within the bilayer.
Findings: KEIF transitions from a disordered to a more structured state, notably increasing α-helical content upon adsorption to lipid bilayers. The peptide resides primarily in the hydrophobic tail region of the bilayer, where it may displace lipids. Electrostatic interactions, modulated by bilayer charge and ionic strength, play a critical role. These results suggest that KEIF's conformational changes and bilayer interactions can be integral to its potential modulatory role in MgtA function within the plasma membrane. This research highlights the importance of surface-induced structural transitions in intrinsically disordered proteins and their implications for membrane protein modulation.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marie Skepö reports financial support was provided by Lund University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)