Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution.

Publication Type:

Journal Article


Science, Volume 329, Issue 5988, p.182-6 (2010)


Amino Acid Sequence, Binding Sites, Calcium, Crystallography, X-Ray, Humans, Ion Channel Gating, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, Ligands, Models, Molecular, Molecular Sequence Data, Mutant Proteins, Patch-Clamp Techniques, Protein Conformation, Protein Folding, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Subunits, Sodium


<p>High-conductance voltage- and Ca2+-activated K+ (BK) channels encode negative feedback regulation of membrane voltage and Ca2+ signaling, playing a central role in numerous physiological processes. We determined the x-ray structure of the human BK Ca2+ gating apparatus at a resolution of 3.0 angstroms and deduced its tetrameric assembly by solving a 6 angstrom resolution structure of a Na+-activated homolog. Two tandem C-terminal regulator of K+ conductance (RCK) domains from each of four channel subunits form a 350-kilodalton gating ring at the intracellular membrane surface. A sequence of aspartic amino acids that is known as the Ca2+ bowl, and is located within the second of the tandem RCK domains, creates four Ca2+ binding sites on the outer perimeter of the gating ring at the "assembly interface" between RCK domains. Functionally important mutations cluster near the Ca2+ bowl, near the "flexible interface" between RCK domains, and on the surface of the gating ring that faces the voltage sensors. The structure suggests that the Ca2+ gating ring, in addition to regulating the pore directly, may also modulate the voltage sensor.</p>