title: Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel.
abstract: The gating ring-forming RCK domain regulates channel gating in response to various cellular chemical stimuli in eukaryotic Slo channel families and the majority of ligand-gated prokaryotic K(+) channels and transporters. Here we present structural and functional studies of a dual RCK-containing, multi-ligand gated K(+) channel from Geobacter sulfurreducens, named GsuK. We demonstrate that ADP and NAD(+) activate the GsuK channel, whereas Ca(2+) serves as an allosteric inhibitor. Multiple crystal structures elucidate the structural basis of multi-ligand gating in GsuK, and also reveal a unique ion conduction pore with segmented inner helices. Structural comparison leads us to propose a novel pore opening mechanics that is distinct from other K(+) channels.DOI:http://dx.doi.org/10.7554/eLife.00184.001.
authors.affiliation: Department of Physiology ,  University of Texas Southwestern Medical Center ,  Dallas ,  United States.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Kong
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zeng
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.forename: David Bryant
authors.initials: DB
authors.lastname: Sauer
authors.forename: Yeeling
authors.initials: Y
authors.lastname: Lam
authors.forename: Mehabaw Getahun
authors.initials: MG
authors.lastname: Derebe
authors.forename: Youxing
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000244:Adenosine Diphosphate; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D045302:Geobacter / Q000737:chemistry* / Q000378:metabolism; D015640:Ion Channel Gating; D058446:Ligand-Gated Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D058446:Ligand-Gated Ion Channels; D008024:Ligands; D015221:Potassium Channels; D011994:Recombinant Proteins; D009243:NAD; D000244:Adenosine Diphosphate; D002118:Calcium