8vc6

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Voltage gated potassium ion channel Kv1.2 in Potassium

Structural highlights

8vc6 is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.17Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KCNA2_RAT Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.[1]

Publication Abstract from PubMed

We present near-atomic-resolution cryo-EM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 A, 2.5 A, 3.2 A, and 2.9A. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2-2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin alpha-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na(+) solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na(+) solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.

Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting.,Wu Y, Yan Y, Yang Y, Bian S, Rivetta A, Allen K, Sigworth FJ bioRxiv [Preprint]. 2024 Mar 19:2023.06.02.543446. doi: , 10.1101/2023.06.02.543446. PMID:37398110[2]

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

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References

  1. Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J. Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature. 1995 Aug 31;376(6543):737-45. PMID:7544443 doi:http://dx.doi.org/10.1038/376737a0
  2. Wu Y, Yan Y, Yang Y, Bian S, Rivetta A, Allen K, Sigworth FJ. Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting. bioRxiv [Preprint]. 2024 Mar 19:2023.06.02.543446. PMID:37398110 doi:10.1101/2023.06.02.543446

Contents


PDB ID 8vc6

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