title: Domain structure and conformational changes in rat KV2.1 ion channel.
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.
authors.affiliation: Saint Petersburg State University, Saint Petersburg, 199034, Russia.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Grizel
authors.forename: Anna
authors.initials: A
authors.lastname: Popinako
authors.forename: Marina A
authors.initials: MA
authors.lastname: Kasimova
authors.forename: Louisa
authors.initials: L
authors.lastname: Stevens
authors.forename: Maria
authors.initials: M
authors.lastname: Karlova
authors.forename: Mikhail M
authors.initials: MM
authors.lastname: Moisenovich
authors.forename: Olga S
authors.initials: OS
authors.lastname: Sokolova
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D051669:Shab Potassium Channels / Q000737:chemistry* / Q000235:genetics*; D014709:Vero Cells
chemical_list: C496991:Kcnb1 protein, rat; D051669:Shab Potassium Channels