Key result
Disruption of the helical domain between residues 423-437 in the calmodulin binding domain abolishes constitutive association with Ca2+-free calmodulin and results in SK channels no longer gated by Ca2+.
Population
Rat SK2 channels (calmodulin binding domain, residues 396-487)
Comparison
Disruption of the helical domain vs Intact helical domain
Design
Preclinical
Authors
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Identifies key structural motif for SK channel gating in animal models; leaves open whether this domain can be therapeutically targeted in humans.
The Ca2+-independent interaction between SK channels and calmodulin depends on a specific helical region in the C-terminus, which is essential for channel gating.
Wissmann et al. (2002) studied this question. Disruption of the helical domain (residues 423-437) in the CaMBD of SK channels vs. Wild-type SK channels was evaluated on Constitutive association of CaMBD with Ca(2+)-free CaM and gating by Ca(2+). Disruption of the helical domain between residues 423-437 in the calmodulin binding domain abolishes constitutive association with Ca2+-free calmodulin and results in SK channels no longer gated by Ca2+.
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