title: Assembly of voltage-gated potassium channels. Conserved hydrophilic motifs determine subfamily-specific interactions between the alpha-subunits.
abstract: Voltage-gated potassium (K+) channels are assembled by four identical or homologous alpha-subunits to form a tetrameric complex with a central conduction pore for potassium ions. Most of the cloned genes for the alpha-subunits are classified into four subfamilies: Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw), and Kv4 (Shal). Subfamily-specific assembly of heteromeric K+ channel complexes has been observed in vitro and in vivo, which contributes to the diversity of K+ currents. However, the molecular codes that mediate the subfamily-specific association remain unknown. To understand the molecular basis of the subfamily-specific assembly, we tested the protein-protein interactions of different regions of alpha-subunits. We report here that the cytoplasmic NH2-terminal domains of Kv1, Kv2, Kv3, and Kv4 subfamilies each associate to form homomultimers. Using the yeast two-hybrid system and eight K+ channel genes, two genes (one isolated from rat and one from Drosophila) from each subfamily, we demonstrated that the associations to form heteromultimers by the NH2-terminal domains are strictly subfamily-specific. These subfamily-specific associations suggest a molecular basis for the selective formation of heteromultimeric channels in vivo.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: Y N
authors.initials: YN
authors.lastname: Jan
authors.forename: L Y
authors.initials: LY
authors.lastname: Jan
authors.forename: M
authors.initials: M
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D017124:Conserved Sequence; D006224:Cricetinae; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry*; D051381:Rats
chemical_list: D015221:Potassium Channels