Single particle image reconstruction of the human recombinant Kv2.1 channel.

Biophysical Journal
Brian AdairMark Yeager

Abstract

Kv2.1 channels are widely expressed in neuronal and endocrine cells and generate slowly activating K+ currents, which contribute to repolarization in these cells. Kv2.1 is expressed at high levels in the mammalian brain and is a major component of the delayed rectifier current in the hippocampus. In addition, Kv2.1 channels have been implicated in the regulation of membrane repolarization, cytoplasmic calcium levels, and insulin secretion in pancreatic beta-cells. They are therefore an important drug target for the treatment of Type II diabetes mellitus. We used electron microscopy and single particle image analysis to derive a three-dimensional density map of recombinant human Kv2.1. The tetrameric channel is egg-shaped with a diameter of approximately 80 A and a long axis of approximately 120 A. Comparison to known crystal structures of homologous domains allowed us to infer the location of the cytoplasmic and transmembrane assemblies. There is a very good fit of the Kv1.2 crystal structure to the assigned transmembrane assembly of Kv2.1. In other low-resolution maps of K+ channels, the cytoplasmic N-terminal and transmembrane domains form separate rings of density. In contrast, Kv2.1 displays contiguous density that connects...Continue Reading

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Citations

Jul 9, 2008·European Biophysics Journal : EBJ·D Wray
Oct 7, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Anastasia V Pischalnikova, Olga S Sokolova
Apr 27, 2011·The Journal of General Physiology·Danielle MandikianJames S Trimmer
May 9, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Durga P MohapatraJames S Trimmer
Jul 24, 2014·Cellular and Molecular Life Sciences : CMLS·Shao-Nian YangPer-Olof Berggren
Sep 27, 2014·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Anastasia GrizelOlga S Sokolova
Jul 30, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Shuang HaoBo Jiang
Jun 27, 2015·PloS One·Kai HeElias Aizenman

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