9g9v

Structure of the human two pore domain potassium ion channel TASK-3 (K2P9.1)

spinqualitylabelsall models 9g9v, resolution 3.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9g9v is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.32Å Ligands: K, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease KCNK9_HUMAN Intellectual deficit, Birk-Barel type. Birk-Barel mental retardation dysmorphism syndrome (BIBAS) [MIM:612292: A syndrome characterized by mental retardation, hypotonia, hyperactivity, and facial dysmorphism. Note=The disease is caused by mutations affecting the gene represented in this entry. Function KCNK9_HUMAN pH-dependent, voltage-insensitive, background potassium channel protein. Publication Abstract from PubMed TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K(+) channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders. A previous crystal structure of TASK-1 revealed a lower "X-gate" as a hotspot for missense gain-of-function (GoF) mutations associated with DDSA (developmental delay with sleep apnea). However, the mechanisms of gating in TASK channels are still not fully understood. Here, we resolve structures for both human TASK-1 and TASK-3 by cryoelectron microscopy (cryo-EM), as well as a recurrent TASK-3 variant (G236R) associated with KCNK9 imprinting syndrome (KIS) (formerly known as Birk-Barel syndrome). Combined with functional studies of the X-gating mechanism, we provide evidence for how a highly conserved gating mechanism becomes defective in disease, and also provide further insight into the pathway of conformational changes that underlie the pH-dependent inhibition of TASK channel activity. Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease.,Hall PR, Jouen-Tachoire T, Schewe M, Proks P, Baukrowitz T, Carpenter EP, Newstead S, Rodstrom KEJ, Tucker SJ Structure. 2024 Nov 27:S0969-2126(24)00495-7. doi: 10.1016/j.str.2024.11.005. PMID:39637865 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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