Structural insights into neuronal K+ channel-calmodulin complexes
Department of Biochemistry and Molecular Pharmacology
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, Karen; Shandilya, Shivender; Blaustein, Robert O.; Schiffer, Celia A.; and Kobertz, William R., "Structural insights into neuronal K+ channel-calmodulin complexes" (2012). Biochemistry and Molecular Pharmacology Publications and Presentations. Paper 145.