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Structure paper

TitleStructural basis for pH gating of the two-pore domain K channel TASK2.
Journal, issue, pagesNature, Vol. 586, Issue 7829, Page 457-462, Year 2020
Publish dateSep 30, 2020
AuthorsBaobin Li / Robert A Rietmeijer / Stephen G Brohawn /
PubMed AbstractTASK2 (also known as KCNK5) channels generate pH-gated leak-type K currents to control cellular electrical excitability. TASK2 is involved in the regulation of breathing by chemosensory neurons of ...TASK2 (also known as KCNK5) channels generate pH-gated leak-type K currents to control cellular electrical excitability. TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem and pH homeostasis by kidney proximal tubule cells. These roles depend on channel activation by intracellular and extracellular alkalization, 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.
External linksNature / PubMed:32999458 / PubMed Central
MethodsEM (single particle)
Resolution3.45 - 3.52 Å
Structure data

21843

6wlv

EMDB-21843, PDB-6wlv:
TASK2 in MSP1D1 lipid nanodisc at pH 6.5
Method: EM (single particle) / Resolution: 3.45 Å

21846

6wm0

EMDB-21846, PDB-6wm0:
TASK2 in MSP1D1 lipid nanodisc at pH 8.5
Method: EM (single particle) / Resolution: 3.52 Å

Chemicals

ChemComp-K:
Unknown entry

Source
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN / Potassium ion channel / K2P channel

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