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Structural insights into neuronal K+ channel-calmodulin complexes.

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.

SUBMITTER: Mruk K

PROVIDER: S-EPMC3427091 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Structural insights into neuronal K+ channel-calmodulin complexes.

Mruk Karen K Shandilya Shiven M D SM Blaustein Robert O RO Schiffer Celia A CA Kobertz William R WR

Proceedings of the National Academy of Sciences of the United States of America 20120806 34

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 d ...[more]

PMID: 22869708

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