3G43

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

Summary for 3G43

• Entry DOI: 10.2210/pdb3g43/pdb
• Related: 2F3Y
• Descriptor: Calmodulin, Voltage-dependent L-type calcium channel subunit alpha-1C, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: calmodulin-bound, coiled coil, calcium channel, acetylation, calcium, methylation, phosphoprotein, polymorphism, ubl conjugation, alternative splicing, brugada syndrome, calcium transport, disease mutation, glycoprotein, ion transport, ionic channel, membrane, transmembrane, transport, voltage-gated channel, metal binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane ; Multi-pass membrane protein : Q13936
• Total number of polymer chains: 6
• Total formula weight: 86160.31

Authors

Fallon, J.L.,Quiocho, F.A. (deposition date: 2009-02-03, release date: 2009-03-03, Last modification date: 2024-02-21)

Primary citation

Fallon, J.L.,Baker, M.R.,Xiong, L.,Loy, R.E.,Yang, G.,Dirksen, R.T.,Hamilton, S.L.,Quiocho, F.A.
Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+{middle dot}calmodulins.
Proc.Natl.Acad.Sci.USA, 106:5135-5140, 2009

PubMed 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.

PubMed: 19279214
DOI: 10.1073/pnas.0807487106

Experimental method

X-RAY DIFFRACTION (2.1 Å)