Crystal Structure of the Human Two-Pore Domain Potassium Channel K2P1

• Published in: Science (American Association for the Advancement of Science) Vol. 335; no. 6067; pp. 432 - 436
• Main Authors: Miller, Alexandria N., Long, Stephen B.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 27-01-2012; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Amino acids; Biological and medical sciences; Carbon; Cell Membrane - chemistry; Cell membranes; Channels; Crystal structure; Crystalline structure; Crystallization; Crystallography, X-Ray; Dimers; Electron density; Fundamental and applied biological sciences. Psychology; Gating and risering; Human; Humans; Ion Channel Gating; Ions; Lipid Bilayers - chemistry; Lipids; Membrane Potentials; Models, Molecular; Molecular biophysics; Molecular Sequence Data; Potassium; Potassium - metabolism; Potassium Channels, Tandem Pore Domain - chemistry; Potassium Channels, Tandem Pore Domain - metabolism; Protein Conformation; Protein Multimerization; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Stimuli; Structure in molecular biology; Human; Inorganic cation; Monovalent cation; Ionic channel; Potassium ion; Crystalline structure
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1213274

Two-pore domain potassium (K⁺) channels (K2P channels) control the negative resting potential of eukaryotic cells and regulate cell excitability by conducting K⁺ ions across the plasma membrane.Here, we present the 3.4 angstrom resolution crystal structure of a human K2P channel, K2P1 (TWIK-1).Unlike other K⁺ channel structures, K2P1 is dimeric. An extracellular cap domain located above the selectivity filter forms an ion pathway in which K ions flow through side portals. Openings within the transmembrane region expose the pore to the lipid bilayer and are filled with electron density attributable to alkyl chains. An interfacial helix appears structurally poised to affect gating. The structure lays a foundation to further investigate how K2P channels are regulated by diverse stimuli.