Structure
Volume 13, Issue 12, December 2005, Pages 1881-1886
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Article
Structure of Calmodulin Bound to the Hydrophobic IQ Domain of the Cardiac Cav1.2 Calcium Channel

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Summary

Ca2+-dependent inactivation (CDI) and facilitation (CDF) of the CaV1.2 Ca2+ channel require calmodulin binding to a putative IQ motif in the carboxy-terminal tail of the pore-forming subunit. We present the 1.45 Å crystal structure of Ca2+-calmodulin bound to a 21 residue peptide corresponding to the IQ domain of CaV1.2. This structure shows that parallel binding of calmodulin to the IQ domain is governed by hydrophobic interactions. Mutations of residues I1672 and Q1673 in the peptide to alanines, which abolish CDI but not CDF in the channel, do not greatly alter the structure. Both lobes of Ca2+-saturated CaM bind to the IQ peptide but isoleucine 1672, thought to form an intramolecular interaction that drives CDI, is buried. These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF.

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