title: A mechanism of regulating transmembrane potassium flux through a ligand-mediated conformational switch.
abstract: The regulation of cation content is critical for cell growth. However, the molecular mechanisms that gate the systems that control K+ movements remain unclear. KTN is a highly conserved cytoplasmic domain present ubiquitously in a variety of prokaryotic and eukaryotic K+ channels and transporters. Here we report crystal structures for two representative KTN domains that reveal a dimeric hinged assembly. Alternative ligands NAD+ and NADH block or vacate, respectively, the hinge region affecting the dimer's conformational flexibility. Conserved, surface-exposed hydrophobic patches that become coplanar upon hinge closure provide an assembly interface for KTN tetramerization. Mutational analysis using the KefC system demonstrates that this domain directly interacts with its respective transmembrane constituent, coupling ligand-mediated KTN conformational changes to the permease's activity.
authors.affiliation: Structural Biology Laboratory, Salk Institute and Division of Biology, University of California, San Diego, 92037, USA.
authors.forename: Tarmo P
authors.initials: TP
authors.lastname: Roosild
authors.forename: Samantha
authors.initials: S
authors.lastname: Miller
authors.forename: Ian R
authors.initials: IR
authors.lastname: Booth
authors.forename: Senyon
authors.initials: S
authors.lastname: Choe
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins; D008024:Ligands; D008027:Light; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008024:Ligands; D015221:Potassium Channels; D009243:NAD; C069287:KefC protein, E coli; D011188:Potassium