Referenced in: none

Automatically associated channels: Kv2.1

Title: Domain structure and conformational changes in rat KV2.1 ion channel.

Authors: Anastasia Grizel, Anna Popinako, Marina A Kasimova, Louisa Stevens, Maria Karlova, Mikhail M Moisenovich, Olga S Sokolova

Journal, date & volume: J Neuroimmune Pharmacol, 2014 Dec , 9, 727-39

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25256718

Abstract
Voltage-gated potassium Kv2.1 channels are widely distributed in the central nervous system, specifically in neuroendocrine and endocrine cells. Their cytoplasmic C-termini are large and carry out many important functions. Here we provide the first direct structural evidence that each C-terminal part within the Kv2.1 ion channel is formed by two distinct domains (Kv2 and CTA). We expressed and purified two C-terminal truncation mutants of a rat Kv2.1 channel, lacking the entire C-termini or the CTA domain. Single particle electron microscopy was used to obtain three-dimensional reconstructions of purified C-terminal Kv2.1 mutants at 2.0 and 2.4 nm resolution. Comparison of these structures to each other and to the low-resolution EM structure of the full-length Kv2.1 channel revealed the exact locations of cytoplasmic Kv2 and CTA domains within the tetramer. Four Kv2 domains envelop the N-terminal T1 domain. The tetramer of the CTA domains underlies the Kv2-T1 complex and may also affect the channel's surface expression. Subsequent molecular dynamics simulation and homology modeling produced open and closed structural models of the membrane part of the Kv2.1 channel.