The M4 Transmembrane α-Helix Contributes Differently to Both the Maturation and Function of Two Prokaryotic Pentameric Ligand-gated Ion Channels.

The Journal of Biological Chemistry
Camille M HénaultJohn E Baenziger

Abstract

The role of the outermost transmembrane α-helix in both the maturation and function of the prokaryotic pentameric ligand-gated ion channels, GLIC and ELIC, was examined by Ala scanning mutagenesis, deletion mutations, and mutant cycle analyses. Ala mutations at the M4-M1/M3 interface lead to loss-of-function phenotypes in GLIC, with the largest negative effects occurring near the M4 C terminus. In particular, two aromatic residues at the M4 C terminus form a network of π-π and/or cation-π interactions with residues on M3 and the β6-β7 loop that is essential for both maturation and function. M4-M1/M3 interactions appear to be optimized in GLIC with even subtle structural changes at this interface leading to detrimental effects. In contrast, mutations along the M4-M1/M3 interface of ELIC typically lead to gain-of-function phenotypes, suggesting that these interactions in ELIC are not optimized for channel function. In addition, no cluster of interacting residues involving the M4 C terminus, M3, and the β6-β7 loop was found, suggesting that the M4 C terminus plays little role in ELIC maturation or function. This study shows that M4 makes distinct contributions to the maturation and gating of these two closely related homologs, sug...Continue Reading

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Citations

Mar 16, 2017·ELife·Anaïs MennyPierre-Jean Corringer
Sep 8, 2018·BMC Neuroscience·Bijun Tang, Sarah C R Lummis
Oct 9, 2019·Nature Chemical Biology·Camille M HénaultChris Ulens
Apr 21, 2020·Biochimica Et Biophysica Acta. Biomembranes·Mackenzie J Thompson, John E Baenziger
Jun 23, 2021·The Journal of Biological Chemistry·Akshay SridharChris Ulens
Nov 10, 2017·ACS Chemical Neuroscience·James Cory-WrightSarah C R Lummis
May 5, 2020·ACS Chemical Neuroscience·Ana R G M da Costa CoutoSarah C R Lummis
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Nov 18, 2020·ACS Chemical Neuroscience·Benjamin W BakerSarah C R Lummis
Mar 6, 2019·ACS Chemical Neuroscience·Susanne MesoySarah C R Lummis

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