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Ion occupancy of the selectivity filter controls opening of a cytoplasmic gate in the K2P channel TALK-2

dc.contributor.authorNeelsen, Lea C.
dc.contributor.authorRiel, Elena B.
dc.contributor.authorRinné, Susanne
dc.contributor.authorSchmid, Freya-Rebecca
dc.contributor.authorJürs, Björn C.
dc.contributor.authorBedoya, Mauricio
dc.contributor.authorLanger, Jan P.
dc.contributor.authorEymsh, Bisher
dc.contributor.authorKiper, Aytug K.
dc.contributor.authorCordeiro, Sönke
dc.contributor.authorDecher, Niels
dc.contributor.authorBaukrowitz, Thomas
dc.contributor.authorSchewe, Marcus
dc.date.accessioned2024-10-03T14:10:46Z
dc.date.available2024-10-03T14:10:46Z
dc.date.issued2024
dc.identifier.urihttp://repositorio.ucm.cl/handle/ucm/5691
dc.description.abstractTwo-pore domain K+ (K2P) channel activity was previously thought to be controlled primarily via a selectivity filter (SF) gate. However, recent crystal structures of TASK-1 and TASK-2 revealed a lower gate at the cytoplasmic pore entrance. Here, we report functional evidence of such a lower gate in the K2P channel K2P17.1 (TALK-2, TASK-4). We identified compounds (drugs and lipids) and mutations that opened the lower gate allowing the fast modification of pore cysteine residues. Surprisingly, stimuli that directly target the SF gate (i.e., pHe., Rb+ permeation, membrane depolarization) also opened the cytoplasmic gate. Reciprocally, opening of the lower gate reduced the electric work to open the SF via voltage driven ion binding. Therefore, it appears that the SF is so rigidly locked into the TALK-2 protein structure that changes in ion occupancy can pry open a distant lower gate and, vice versa, opening of the lower gate concurrently promote SF gate opening. This concept might extent to other K+ channels that contain two gates (e.g., voltage-gated K+ channels) for which such a positive gate coupling has been suggested, but so far not directly demonstrated.es_CL
dc.language.isoenes_CL
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
dc.sourceNature Communications, 15, 7545es_CL
dc.titleIon occupancy of the selectivity filter controls opening of a cytoplasmic gate in the K2P channel TALK-2es_CL
dc.typeArticlees_CL
dc.ucm.facultadFacultad de Medicinaes_CL
dc.ucm.indexacionScopuses_CL
dc.ucm.indexacionIsies_CL
dc.ucm.urinature.ucm.elogim.com/articles/s41467-024-51812-wes_CL
dc.ucm.doidoi.org/10.1038/s41467-024-51812-wes_CL


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Atribución-NoComercial-SinDerivadas 3.0 Chile
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