Journal
CHANNELS
Volume 5, Issue 1, Pages 1-3Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/chan.5.1.14818
Keywords
Slo1; RCK domain; structure; calcium; gating ring; crystallography
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The large conductance, voltage- and Ca2+-activated K+ channel (BK or Slo1) is widely expressed in mammalian cells/tissues (e. g. neurons, skeletal and smooth muscles, exocrine cells, the inner ear) and regulates action potential firing/neurotransmission, muscle contraction and secretory processes. The large ionic conductance and unusual, bimodal stimulus-driven gating behavior of this channel have long intrigued membrane biophysicists, and recent structure/function analyses have provided increasingly detailed insights into the molecular features of the channel that regulate its activation. Now, in two complementary articles published by the groups of Rod MacKinnon and Youxing Jiang, high resolution x-ray crystal structures of the human BK channel's large cytoplasmic domain have been solved in both the absence and presence of bound Ca2+, conditions that would be expected to promote the resting and activated conformations, respectively, of this large domain. Given the regulatory importance of the cytosolic domain on BK channel gating, these new experimentally determined structures reveal a number of key insights, including: 1) the physical arrangement and interactions of the tandem RCK1 and RCK2 domains within a single channel subunit, 2) the assembly of the four large cytoplasmic domains into a symmetric, tetrameric complex, 3) the organization, assembly and interactions of the individual RCK1 and RCK2 domains into a symmetric gating ring complex for the holo-channel, and 4) the structural elements underlying the regions critical for divalent metal ion binding (i.e. Ca2+ and Mg2+) and the potential structural mechanisms by which they influence opening of the ion conduction pore.
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