Open AccessStructural basis for pH gating of the two-pore domain K+ channel TASK2
Author(s) -
Baobin Li,
Robert A. Rietmeijer,
Stephen G. Brohawn
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2770-2
Subject(s) - gating , chemistry , biophysics , intracellular , extracellular , protonation , membrane potential , nucleus , neuroscience , biochemistry , biology , ion , organic chemistry
TASK2 (also known as KCNK5) channels generate pH-gated leak-type K + currents to control cellular electrical excitability 1-3 . TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem 4-6 and pH homeostasis by kidney proximal tubule cells 7,8 . These roles depend on channel activation by intracellular and extracellular alkalization 3,8,9 , but the mechanistic basis for TASK2 gating by pH is unknown. Here we present cryo-electron microscopy structures of Mus musculus TASK2 in lipid nanodiscs in open and closed conformations. We identify two gates, distinct from previously observed K + channel gates, controlled by stimuli on either side of the membrane. Intracellular gating involves lysine protonation on inner helices and the formation of a protein seal between the cytoplasm and the channel. Extracellular gating involves arginine protonation on the channel surface and correlated conformational changes that displace the K + -selectivity filter to render it nonconductive. These results explain how internal and external protons control intracellular and selectivity filter gates to modulate TASK2 activity.