Title
Structural insights into neuronal K+ channel-calmodulin complexes
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2012-08-21
Document Type
Article
Subjects
Calmodulin; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Tetraethylammonium
Disciplines
Biochemistry, Biophysics, and Structural Biology | Chemistry
Abstract
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.
DOI of Published Version
10.1073/pnas.1207606109
Source
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
Journal/Book/Conference Title
Proceedings of the National Academy of Sciences of the United States of America
Related Resources
PubMed ID
22869708
Repository Citation
Mruk K, Shandilya S, Blaustein RO, Schiffer CA, Kobertz WR. (2012). Structural insights into neuronal K+ channel-calmodulin complexes. Biochemistry and Molecular Biotechnology Publications. https://doi.org/10.1073/pnas.1207606109. Retrieved from https://escholarship.umassmed.edu/bmp_pp/145
Comments
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.