Molecular Overlap in the Regulation of SK Channels by Small Molecules and Phosphoinositides

Authors

Miao Zhang, Chapman UniversityFollow
Xuan-Yu Meng, Virginia Commonwealth UniversityFollow
Ji-fang Zhang, Thomas Jefferson UniversityFollow
Meng Cui, Virginia Commonwealth University
Diomedes E. Logothetis, Virginia Commonwealth UniversityFollow

Document Type

Article

Publication Date

7-10-2015

Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.

Comments

This article was originally published in Science Advances, volume 1, in 2015. DOI: 10.1126/sciadv.1500008

Recommended Citation

M. Zhang, X.-Y. Meng, J.-f. Zhang, M. Cui, D. E. Logothetis, Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides. Sci. Adv. 1, e1500008 (2015).
DOI:10.1126/sciadv.1500008

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License