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Description
In the activated state of small-conductance Ca2+-activated potassium (SK) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates SK2a and SK3 channel activity but not the SK1 and IK subtypes. Here, we report that the subtype-selectivity of CyPPA relies on the HA/HB helices. Mutating residues in the HA (V420) and HB (K467) helices of SK2a channels to their equivalent residues in IK channels diminished the potency of CyPPA. CyPPA elicited prominent responses on mutant IK channels with an arginine residue in the HB helix substituted for its equivalent lysine residue in the SK2a channels (R355K). SK1 channels harboring a three-amino-acid insertion upstream of the cognate R438 residues in the HB helix showed no response to CyPPA, whereas the deletion mutant (SK1_DA434/Q435/K436) became sensitive to CyPPA. In molecular dynamics simulations, CyPPA docked between calmodulin and the HA/HB helices widens the cytoplasmic gate of SK2a channels.
Publication Date
3-25-2021
Keywords
PDB file, CyPPA, Docked, SK2
Disciplines
Medicinal and Pharmaceutical Chemistry | Medicinal-Pharmaceutical Chemistry | Other Pharmacy and Pharmaceutical Sciences
Recommended Citation
Zhang M, Cui M. Data for "Subtype-selective Positive Modulation of SK channels Depends on the HA/HB Helices" [data set]. 2021. https://doi.org/10.36837/chapman.000233
Peer Reviewed
1
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Medicinal and Pharmaceutical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Other Pharmacy and Pharmaceutical Sciences Commons