Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains

• Published in: Nature structural & molecular biology Vol. 15; no. 11; pp. 1152 - 1159
• Main Authors: Yang, Huanghe, Shi, Jingyi, Zhang, Guohui, Yang, Junqiu, Delaloye, Kelli, Cui, Jianmin
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2008; Nature Publishing Group
• Subjects: Amino Acid Sequence; Amino acids; Animals; Binding Sites; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; Humans; Ion Channel Gating - physiology; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - chemistry; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - genetics; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - metabolism; Life Sciences; Magnesium - chemistry; Membrane Biology; Mice; Models, Molecular; Molecular biology; Molecular Sequence Data; Molecular structure; Patch-Clamp Techniques; Potassium Channels - chemistry; Potassium Channels - metabolism; Protein Structure; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; Sensors; Sequence Alignment
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1507

The voltage-sensor and RCK1 domains of BK channels act synergistically to sense electric and chemical signals. New data now indicate that the Mg 2+ -mediated interactions between these domains occurs between channel subunits, suggesting a structural arrangement that differs from other potassium channels. The voltage-sensor domain (VSD) and the ligand sensor (cytoplasmic domain) of BK channels synergistically control channel activities, thereby integrating electrical and chemical signals for cell function. Studies show that intracellular Mg 2+ mediates the interaction between these sensory domains to activate the channel through an electrostatic interaction with the VSD. Here we report that Mg 2+ binds to a site that consists of amino acid side chains from both the VSD (Asp99 and Asn172) and the cytoplasmic domain (Glu374 and Glu399). For each Mg 2+ binding site, the residues in the VSD and those in the cytoplasmic domain come from neighboring subunits. These results suggest that the VSD and the cytoplasmic domains from different subunits may interact during channel gating, and the packing of VSD or the RCK1 domain to the pore in BK channels differ from that in Kv1.2 or MthK channels.