Nature. 2010 Jul 15;466(7304):393-7.

Yunkun Wu, Yi Yang, Sheng Ye , Youxing Jiang*

Abstract

Large-conductance Ca²⁺gated K⁺ (BK) channels are essential for many biological processes such as smooth muscle contraction and neurotransmitter release. This group of channels can be activated synergistically by both voltage and intracellular Ca²⁺, with the large carboxy-terminal intracellular portion being responsible for Ca²⁺ sensing. Here we present the crystal structure of the entire cytoplasmic region of the human BK channel in a Ca²⁺ free state. The structure reveals four intracellular subunits, each comprising two tandem RCK domains, assembled into a gating ring similar to that seen in the MthK channel and probably representing its physiological assembly. Three Ca²⁺ binding sites including the Ca²⁺ bowl are mapped onto the structure based on mutagenesis data. The Ca²⁺ bowl, located within the second RCK domain, forms an EF-hand-like motif and is strategically positioned close to the assembly interface between two subunits. The other two Ca²⁺ (or Mg²⁺) binding sites, Asp 367 and Glu 374/Glu 399, are located on the first RCK domain. The Asp 367 site has high Ca²⁺ sensitivity and is positioned in the groove between the amino- and carboxyterminal subdomains of RCK1, whereas the low-affinity Mg21-binding Glu 374/Glu 399 site is positioned on the upper plateau of the gating ring and close to the membrane. Our structure also contains the linker connecting the transmembrane and intracellulardomains, allowing us to dock a voltage-gated K⁺ channel pore of known structure onto the gating ring with reasonable accuracy and generate a structural model for the full BK channel.

Text link：http://www.nature.com/nature/journal/v466/n7304/full/nature09252.html