Selectivity filter modalities and rapid inactivation of the hERG1 channel
Copyright policy )Selectivity filter modalities and rapid inactivation of the hERG1 channel
Significance The familial mutations impacting repolarization K + currents conducted by the hERG1 channel are significant determinants of arrhythmogenicity. Here, we show how the arrhythmogenic gain-of-function mutation (N629D) in the pore domain impairs channel selectivity and inactivation by shifting complex conformational equilibria between the conductive and nonconductive states of the selectivity filter and by impacting filter modalities. This study highlights notable differences in the permeation and inactivation dynamics in a human channel that displays a nonconventional selectivity filter.
- Libin Cardiovascular Institute of Alberta Canada
- University of California, San Francisco United States
- University of California, Davis United States
- University of California System United States
- University of Calgary, Department of Biological Sciences Canada
570, Protein Structure, Secondary, ERG1 Potassium Channel, 1.1 Normal biological development and functioning, Medical Physiology, Amino Acid Motifs, Mutation, Missense, human ether-a-go-go channel, Cardiovascular, 530, Protein Structure, Secondary, Protein Domains, Genetics, Humans, Biomedical and Clinical Sciences, ion channels, molecular dynamics, long-QT syndrome, Kinetics, Long QT Syndrome, Networking and Information Technology R&D (NITRD), Gain of Function Mutation, Physical Sciences, Mutation, Potassium, Generic health relevance, Missense, human ether-á-go-go channel
570, Protein Structure, Secondary, ERG1 Potassium Channel, 1.1 Normal biological development and functioning, Medical Physiology, Amino Acid Motifs, Mutation, Missense, human ether-a-go-go channel, Cardiovascular, 530, Protein Structure, Secondary, Protein Domains, Genetics, Humans, Biomedical and Clinical Sciences, ion channels, molecular dynamics, long-QT syndrome, Kinetics, Long QT Syndrome, Networking and Information Technology R&D (NITRD), Gain of Function Mutation, Physical Sciences, Mutation, Potassium, Generic health relevance, Missense, human ether-á-go-go channel
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