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Gating Domain of Calcium-Activated Potassium Channel with Calcium and Calmodulin

  1. Maria A Schumacher

Published Online: 15 DEC 2011

DOI: 10.1002/9781119951438.eibc0506

Encyclopedia of Inorganic and Bioinorganic Chemistry

Encyclopedia of Inorganic and Bioinorganic Chemistry

How to Cite

Schumacher, M. A. 2011. Gating Domain of Calcium-Activated Potassium Channel with Calcium and Calmodulin. Encyclopedia of Inorganic and Bioinorganic Chemistry. .

Author Information

  1. Oregon Health and Science University, Department of Biochemistry and Molecular Biology, Portland, OR, USA

Publication History

  1. Published Online: 15 DEC 2011

Abstract

Small conductance Ca2+-activated K+ channels (SK channels) are voltage-independent and gated solely by increases in intracellular Ca2+ such as that occurs during an action potential. SK channels are heteromeric complexes and consist of pore-forming α-subunits and calmodulin (CaM). CaM is constitutively associated with an intracellular region of the α-subunit immediately C-terminal to the pore, the CaM binding domain (CaMBD). In order to trigger channel opening, Ca2+ must only bind the EF hands in the CaM N-lobe. The 1.60-Å crystal structure of the SK channel Ca2+/CaM/CaMBD complex reveals that the CaMBD forms an elongated dimer with a CaM bound at each end and each CaM wraps around three α-helices, two from one CaMBD subunit and one from the other. The structure also provides a view of both Ca2+-dependent and Ca2+-independent protein interactions; only the CaM N-lobe is calcified while the noncalcified C-lobe is responsible for the CaM/CaMBD constitutive interaction. This structure combined with biochemical data suggests a possible gating mechanism in which Ca2+ binding to each CaM N-lobe exposes its hydrophobic patch, thus allowing it to interact with an adjacent CaMBD monomer. As each N-lobe on adjacent monomers interacts with the other CaMBD C-terminal region, a rotary force would be created between them and transmitted to the attached S6 pore helices in the gate region. In this chemo-mechanical model, two CaMBD dimers would serve as mechanical levers to drive open the channel.

3D Structure

Keywords:

  • K+ channel;
  • SK channel;
  • Ca2+-activated gating;
  • calmodulin;
  • EF hand;
  • functional bipartism