Gating Domain of Calcium-Activated Potassium Channel with Calcium and Calmodulin
Part 9. Calcium
EF-Hand Ca2+-Binding Proteins
Published Online: 15 APR 2006
Copyright © 2006 John Wiley & Sons, Ltd. All rights reserved.
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.
- Published Online: 15 APR 2006
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.
- K+ channel;
- SK channel;
- Ca2+-activated gating;
- EF hand;
- functional bipartism