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

Amanda Eriksson Skog; Nykola C Jones; Linda K Månsson; Jens Preben Morth; Søren Vrønning Hoffmann; Yuri Gerelli; Marie Skepö

doi:10.1016/j.jcis.2024.12.064

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

J Colloid Interface Sci. 2024 Dec 16;683(Pt 1):663-674. doi: 10.1016/j.jcis.2024.12.064. Online ahead of print.

Authors

Amanda Eriksson Skog¹, Nykola C Jones², Linda K Månsson¹, Jens Preben Morth³, Søren Vrønning Hoffmann², Yuri Gerelli⁴, Marie Skepö⁵

Affiliations

¹ Division of Computational Chemistry, Department of Chemistry, Lund University, P.O. Box 124, Lund, 22100, Sweden.
² ISA, Department of Physics & Astronomy, Aarhus University, Aarhus C, 8000, Denmark.
³ Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Kgs. Lyngby, 2800, Denmark.
⁴ Institute for Complex Systems, Consiglio Nazionale delle Ricerche, Piazzale Aldo Moro 5, Roma, 00185, Italy; Department of Physics, Sapienza University of Rome,Piazzale Aldo Moro 2, Roma, 00185, Italy.
⁵ Division of Computational Chemistry, Department of Chemistry, Lund University, P.O. Box 124, Lund, 22100, Sweden. Electronic address: marie.skepo@compchem.lu.se.

PMID: 39706085
DOI: 10.1016/j.jcis.2024.12.064

Abstract

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.

Keywords: Intrinsically disordered proteins; Lipid bilayer; MgtA; Peptide adsorption; Protein-lipid interaction.