Structural insights into neuronal K+ channel-calmodulin complexes

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology



Document Type


Medical Subject Headings

Calmodulin; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Tetraethylammonium


Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds to and modulates a wide variety of ion channels. Despite the large repository of high-resolution structures of CaM bound to peptide fragments derived from ion channels, there is no structural information about CaM bound to a fully folded ion channel at the plasma membrane. To determine the location of CaM docked to a functioning KCNQ K(+) channel, we developed an intracellular tethered blocker approach to measure distances between CaM residues and the ion-conducting pathway. Combining these distance restraints with structural bioinformatics, we generated an archetypal quaternary structural model of an ion channel-CaM complex in the open state. These models place CaM close to the cytoplasmic gate, where it is well positioned to modulate channel function.


Mruk K, Shandilya SM, Blaustein RO, Schiffer CA, Kobertz WR. Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13579-83. DOI 10.1073/pnas.1207606109. Link to article on publisher's site

Co-author Karen Mruk is a student in the Biochemistry & Molecular Pharmacology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

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