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

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.

Related Resources

Link to article in PubMed

PubMed ID

22869708

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