Allosteric mechanism for KCNE1 modulation of KCNQ1 potassium channel activation.
Elife
; 92020 10 23.
Article
em En
| MEDLINE
| ID: mdl-33095155
ABSTRACT
The function of the voltage-gated KCNQ1 potassium channel is regulated by co-assembly with KCNE auxiliary subunits. KCNQ1-KCNE1 channels generate the slow delayed rectifier current, IKs, which contributes to the repolarization phase of the cardiac action potential. A three amino acid motif (F57-T58-L59, FTL) in KCNE1 is essential for slow activation of KCNQ1-KCNE1 channels. However, how this motif interacts with KCNQ1 to control its function is unknown. Combining computational modeling with electrophysiological studies, we developed structural models of the KCNQ1-KCNE1 complex that suggest how KCNE1 controls KCNQ1 activation. The FTL motif binds at a cleft between the voltage-sensing and pore domains and appears to affect the channel gate by an allosteric mechanism. Comparison with the KCNQ1-KCNE3 channel structure suggests a common transmembrane-binding mode for different KCNEs and illuminates how specific differences in the interaction of their triplet motifs determine the profound differences in KCNQ1 functional modulation by KCNE1 versus KCNE3.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação do Canal Iônico
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Canal de Potássio KCNQ1
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Potenciais da Membrana
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2020
Tipo de documento:
Article