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|3g43, resolution 2.10Å ()|
|Gene:||CALM, CALM1, CALM2, CALM3, CALML2, CAM, CAM1, CAM2, CAM3, CAMB, CAMC, CAMIII (Homo sapiens), CACNA1C, CACH2, CACN2, CACNL1A1, CCHL1A1 (Homo sapiens)|
Crystal structure of the calmodulin-bound Cav1.2 C-terminal regulatory domain dimer
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.
Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins., Fallon JL, Baker MR, Xiong L, Loy RE, Yang G, Dirksen RT, Hamilton SL, Quiocho FA, Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5135-40. Epub 2009 Mar 11. PMID:19279214
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Fallon JL, Baker MR, Xiong L, Loy RE, Yang G, Dirksen RT, Hamilton SL, Quiocho FA. Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5135-40. Epub 2009 Mar 11. PMID:19279214
- Fallon JL, Halling DB, Hamilton SL, Quiocho FA. Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel. Structure. 2005 Dec;13(12):1881-6. PMID:16338416 doi:10.1016/j.str.2005.09.021