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7lj4

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Human TRAAK K+ channel FHEIG mutant A270P in a K+ bound conductive conformation

Structural highlights

7lj4 is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.782Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KCNK4_HUMAN Voltage insensitive, instantaneous, outwardly rectifying potassium channel. Outward rectification is reversed at high external K(+) concentrations (By similarity).

Publication Abstract from PubMed

TRAAK is a mechanosensitive two-pore domain K(+) (K2P) channel localized to nodes of Ranvier in myelinated neurons. TRAAK deletion in mice results in mechanical and thermal allodynia, and gain-of-function mutations cause the human neurodevelopmental disorder FHEIG. TRAAK displays basal and stimulus-gated activities typical of K2Ps, but the mechanistic and structural differences between these modes are unknown. Here, we demonstrate that basal and mechanically gated openings are distinguished by their conductance, kinetics, and structure. Basal openings are low conductance, short duration, and due to a conductive channel conformation with the interior cavity exposed to the surrounding membrane. Mechanically gated openings are high conductance, long duration, and due to a channel conformation in which the interior cavity is sealed to the surrounding membrane. Our results explain how dual modes of activity are produced by a single ion channel and provide a basis for the development of state-selective pharmacology with the potential to treat disease.

Physical basis for distinct basal and mechanically gated activity of the human K(+) channel TRAAK.,Rietmeijer RA, Sorum B, Li B, Brohawn SG Neuron. 2021 Sep 15;109(18):2902-2913.e4. doi: 10.1016/j.neuron.2021.07.009. Epub , 2021 Aug 13. PMID:34390650^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rietmeijer RA, Sorum B, Li B, Brohawn SG. Physical basis for distinct basal and mechanically gated activity of the human K(+) channel TRAAK. Neuron. 2021 Sep 15;109(18):2902-2913.e4. PMID:34390650 doi:10.1016/j.neuron.2021.07.009