Structural Basis of Human KCNQ1 Modulation and Gating.
Cell
; 180(2): 340-347.e9, 2020 01 23.
Article
en En
| MEDLINE
| ID: mdl-31883792
ABSTRACT
KCNQ1, also known as Kv7.1, is a voltage-dependent K+ channel that regulates gastric acid secretion, salt and glucose homeostasis, and heart rhythm. Its functional properties are regulated in a tissue-specific manner through co-assembly with beta subunits KCNE1-5. In non-excitable cells, KCNQ1 forms a complex with KCNE3, which suppresses channel closure at negative membrane voltages that otherwise would close it. Pore opening is regulated by the signaling lipid PIP2. Using cryoelectron microscopy (cryo-EM), we show that KCNE3 tucks its single-membrane-spanning helix against KCNQ1, at a location that appears to lock the voltage sensor in its depolarized conformation. Without PIP2, the pore remains closed. Upon addition, PIP2 occupies a site on KCNQ1 within the inner membrane leaflet, which triggers a large conformational change that leads to dilation of the pore's gate. It is likely that this mechanism of PIP2 activation is conserved among Kv7 channels.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Canal de Potasio KCNQ1
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article