8VC4

Voltage gated potassium ion channel Kv1.2 in Sodium

Summary for 8VC4

• Entry DOI: 10.2210/pdb8vc4/pdb
• EMDB information: 43133
• Descriptor: Potassium voltage-gated channel subfamily A member 2 (1 entity in total)
• Functional Keywords: ion channel, sodium bound, membrane protein
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 242366.28

Authors

Wu, Y.,Sigworth, F.J. (deposition date: 2023-12-13, release date: 2024-07-10, Last modification date: 2024-07-17)

Primary citation

Wu, Y.,Yan, Y.,Yang, Y.,Bian, S.,Rivetta, A.,Allen, K.,Sigworth, F.J.
Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting.
Biorxiv, 2024

PubMed Abstract: 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 Å, 2.5 Å, 3.2 Å, and 2.9Å. 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 α-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.

PubMed: 37398110
DOI: 10.1101/2023.06.02.543446

Experimental method

ELECTRON MICROSCOPY (3.17 Å)