A Mechanism of Regulating Transmembrane Potassium Flux through a Ligand-Mediated Conformational Switch

• Published in: Cell Vol. 109; no. 6; pp. 781 - 791
• Main Authors: Roosild, Tarmo P., Miller, Samantha, Booth, Ian R., Choe, Senyon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-06-2002
• Subjects: Amino Acid Sequence; Bacterial Proteins - metabolism; Cell Membrane - metabolism; Cytoplasm - metabolism; Dimerization; DNA Mutational Analysis; Dose-Response Relationship, Drug; Escherichia coli Proteins; Ligands; Light; Models, Molecular; Molecular Sequence Data; NAD - metabolism; Potassium - metabolism; Potassium Channels - metabolism; Protein Conformation; Protein Structure, Tertiary; Scattering, Radiation; Sequence Homology, Amino Acid
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)00768-7

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.