3G43: Crystal structure of the calmodulin-bound Cav1.2 C-terminal regulatory domain dimer

Citation:
Abstract
Voltage-dependent calcium channels (Ca(V)) open in response to changes in membrane potential, but their activity is modulated by Ca(2+) binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot adequately describe CaM's role in the regulation of these channels. We report a unique crystal structure of a 77-residue fragment of the Ca(V)1.2 alpha(1) subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ domains, in complex with Ca(2+).CaM in 2 distinct binding modes. The structure of the Ca(V)1.2 fragment is an unusual dimer of 2 coiled-coiled pre-IQ regions bridged by 2 Ca(2+).CaMs interacting with the pre-IQ regions and a canonical Ca(V)1-IQ-Ca(2+).CaM complex. Native Ca(V)1.2 channels are shown to be a mixture of monomers/dimers and a point mutation in the pre-IQ region predicted to abolish the coiled-coil structure significantly reduces Ca(2+)-dependent inactivation of heterologously expressed Ca(V)1.2 channels.
PDB ID: 3G43Download
MMDB ID: 70013
PDB Deposition Date: 2009/2/3
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 3G43: hexameric; determined by author and by software (PISA)
Molecular Components in 3G43
Label Count Molecule
Proteins (6 molecules)
4
Calmodulin
Molecule annotation
2
Voltage-dependent L-type Calcium Channel Subunit Alpha-1c(Gene symbol: CACNA1C)
Molecule annotation
Chemicals (14 molecules)
1
14
* Click molecule labels to explore molecular sequence information.

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