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Dimerization mechanism of an inverted-topology ion channel in membranes

Melanie Ernst,Esam A. Orabi,R. Stockbridge,J. Faraldo-Gómez,J. Robertson

Published 2023 in Proceedings of the National Academy of Sciences of the United States of America

ABSTRACT

Significance Ion channels are of critical importance in cellular physiology, where selective and properly timed permeation of ions across the membrane is a requirement for ionic homeostasis and excitability. Yet, we often do not understand what dictates proper folding and assembly of ion channels in membranes. Here, we present experimental measurements of the equilibrium assembly of an ion channel complex in membranes, a model system we developed based on the dual-topology fluoride ion channel Fluc, and report the linkage of the stability to buried sodium binding. Parallel computational studies demonstrate that the assembly of this species into dimers is driven by the membrane energetics alone, while sodium binding regulates the conductive state of the dimer.

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