title: Cadmium-cysteine coordination in the BK inner pore region and its structural and functional implications.
abstract: To probe structure and gating-associated conformational changes in BK-type potassium (BK) channels, we examined consequences of Cd(2+) coordination with cysteines introduced at two positions in the BK inner pore. At V319C, the equivalent of valine in the conserved Kv proline-valine-proline (PVP) motif, Cd(2+) forms intrasubunit coordination with a native glutamate E321, which would place the side chains of V319C and E321 much closer together than observed in voltage-dependent K(+) (Kv) channel structures, requiring that the proline between V319C and E321 introduces a kink in the BK S6 inner helix sharper than that observed in Kv channel structures. At inner pore position A316C, Cd(2+) binds with modest state dependence, suggesting the absence of an ion permeation gate at the cytosolic side of BK channel. These results highlight fundamental structural differences between BK and Kv channels in their inner pore region, which likely underlie differences in voltage-dependent gating between these channels.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 zhouy@wustl.edu clingle@morpheus.wustl.edu.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 zhouy@wustl.edu clingle@morpheus.wustl.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lingle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D050505:Mutant Proteins; D021122:Protein Subunits; D002104:Cadmium; D018698:Glutamic Acid; D003545:Cysteine
keywords: BK channels; Cd2+ coordination; K+ channels; Slo1 channels; state dependence
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