The Role of Native Cysteine Residues in the Oligomerization of KCNQ1 Channels

Authors

Alison Bates
Rebecca B Stowe
Elizabeth M Travis
Lauryn E Cook
Carole Dabney-Smith
Gary A Lorigan

Publication Date

6-4-2023

Journal

Biochemical and Biophysical Research Communications

Abstract

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal domain still tetramerize. Therefore, we explored the role of native cysteine residues in a truncated construct of human KCNQ1, amino acids 100-370, by blocking potential interactions of cysteines with a nitroxide based spin label. Mobility of the spin labels was investigated with continuous wave electron paramagnetic resonance (CW-EPR) spectroscopy. The oligomerization state was examined by gel electrophoresis. The data provide information on tetramerization of human KCNQ1 without the C-terminal domain. Specifically, how blocking the side chains of native cysteines residues reduces oligomerization. A better understanding of tetramer formation could provide improved understanding of the molecular etiology of long QT syndrome and other diseases related to KCNQ1.

Keywords

Humans, Potassium Channels, Voltage-Gated, KCNQ1 Potassium Channel, Cysteine, Mutation, Long QT Syndrome, EPR spectroscopy, KCNQ1, Kv channel, Oligomerization, SDS-PAGE

Comments

Associated Data

PMID: 37031592