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

Part 9. Calcium

EF-Hand Ca2+-Binding Proteins

  1. Maria A Schumacher

Published Online: 15 APR 2006

DOI: 10.1002/0470028637.met041

Handbook of Metalloproteins

Handbook of Metalloproteins

How to Cite

Schumacher, M. A. 2006. Gating Domain of Calcium-Activated Potassium Channel with Calcium and Calmodulin. Handbook of Metalloproteins. 9.

Author Information

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

Publication History

  1. Published Online: 15 APR 2006

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