8F1D

Voltage-gated potassium channel Kv3.1 apo

Summary for 8F1D

• Entry DOI: 10.2210/pdb8f1d/pdb
• EMDB information: 28793 28795
• Descriptor: Potassium voltage-gated channel subfamily C member 1, ZINC ION, CHOLESTEROL, ... (4 entities in total)
• Functional Keywords: ion channel, positive modulator, voltage gated, voltage gated potassium channel, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 252945.71

Authors

Chen, Y.,Ishchenko, A. (deposition date: 2022-11-04, release date: 2023-10-25)

Primary citation

Chen, Y.T.,Hong, M.R.,Zhang, X.J.,Kostas, J.,Li, Y.,Kraus, R.L.,Santarelli, V.P.,Wang, D.,Gomez-Llorente, Y.,Brooun, A.,Strickland, C.,Soisson, S.M.,Klein, D.J.,Ginnetti, A.T.,Marino, M.J.,Stachel, S.J.,Ishchenko, A.
Identification and structural and biophysical characterization of a positive modulator of human Kv3.1 channels.
Proc.Natl.Acad.Sci.USA, 120:e2220029120-e2220029120, 2023

PubMed Abstract: Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K) to diffuse across a hydrophobic cell membrane. These unique voltage-gated cation channels detect changes in membrane potential and, upon activation, help to return the depolarized cell to a resting state during the repolarization stage of each action potential. The Kv3 family of potassium channels is characterized by a high activation potential and rapid kinetics, which play a crucial role for the fast-spiking neuronal phenotype. Mutations in the Kv3.1 channel have been shown to have implications in various neurological diseases like epilepsy and Alzheimer's disease. Moreover, disruptions in neuronal circuitry involving Kv3.1 have been correlated with negative symptoms of schizophrenia. Here, we report the discovery of a novel positive modulator of Kv3.1, investigate its biophysical properties, and determine the cryo-EM structure of the compound in complex with Kv3.1. Structural analysis reveals the molecular determinants of positive modulation in Kv3.1 channels by this class of compounds and provides additional opportunities for rational drug design for the treatment of associated neurological disorders.

PubMed: 37812700
DOI: 10.1073/pnas.2220029120

Experimental method

ELECTRON MICROSCOPY (2.94 Å)