title: Role of the KcsA channel cytoplasmic domain in pH-dependent gating.
abstract: The KcsA channel is a representative potassium channel that is activated by changes in pH. Previous studies suggested that the region that senses pH is entirely within its transmembrane segments. However, we recently revealed that the cytoplasmic domain also has an important role, because its conformation was observed to change dramatically in response to pH changes. Here, to investigate the effects of the cytoplasmic domain on pH-dependent gating, we made a chimera mutant channel consisting of the cytoplasmic domain of the KcsA channel and the transmembrane region of the MthK channel. The chimera showed a pH dependency similar to that of KcsA, indicating that the cytoplasmic domain can act as a pH sensor. To identify how this region detects pH, we substituted certain cytoplasmic domain amino acids that are normally negatively charged at pH 7 for neutral ones in the KcsA channels. These mutants opened independently of pH, suggesting that electrostatic charges have a major role in the cytoplasmic domain's ability to sense and respond to pH.
authors: Laboratory for Cell Dynamics Observation, Quantitative Biology Center, RIKEN, Osaka, Japan.
authors: Minako
authors: M
authors: Hirano
authors: Yukiko
authors: Y
authors: Onishi
authors: Toshio
authors: T
authors: Yanagida
authors: Toru
authors: T
authors: Ide
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D008954:Models, Biological; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D050505:Mutant Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel