Molecular Basis of the Membrane Interaction of the β2e Subunit of Voltage-Gated Ca(2+) Channels

Biophysical Journal
Dong-Il KimByung-Chang Suh

Abstract

The auxiliary β subunit plays an important role in the regulation of voltage-gated calcium (CaV) channels. Recently, it was revealed that β2e associates with the plasma membrane through an electrostatic interaction between N-terminal basic residues and anionic phospholipids. However, a molecular-level understanding of β-subunit membrane recruitment in structural detail has remained elusive. In this study, using a combination of site-directed mutagenesis, liposome-binding assays, and multiscale molecular-dynamics (MD) simulation, we developed a physical model of how the β2e subunit is recruited electrostatically to the plasma membrane. In a fluorescence resonance energy transfer assay with liposomes, binding of the N-terminal peptide (23 residues) to liposome was significantly increased in the presence of phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). A mutagenesis analysis suggested that two basic residues proximal to Met-1, Lys-2 (K2) and Trp-5 (W5), are more important for membrane binding of the β2e subunit than distal residues from the N-terminus. Our MD simulations revealed that a stretched binding mode of the N-terminus to PS is required for stable membrane attachment through polar and nonpolar i...Continue Reading

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Citations

Aug 2, 2018·Physiological Reviews·Yasushi OkamuraTakafumi Kawai
Jan 15, 2017·The Journal of General Physiology·Cheon-Gyu ParkByung-Chang Suh
Sep 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hee YeonByung-Chang Suh
Dec 19, 2019·Pflügers Archiv : European journal of physiology·Nadine J OrtnerJörg Striessnig
Apr 24, 2021·Traffic·Rachel ConradPatricia Hidalgo

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