PDBsum entry 3g43

Metal binding protein

PDB id: 3g43

Contents

Protein chains

75 a.a. *

147 a.a. *

68 a.a. *

45 a.a. *

Metals

_CA ×14

Waters ×518

* Residue conservation analysis

PDB id:

3g43

Name:

Metal binding protein

Title:

Crystal structure of the calmodulin-bound cav1.2 c-terminal regulatory domain dimer

Structure:

Calmodulin. Chain: a, b, c, d. Synonym: cam. Engineered: yes. Voltage-dependent l-type calcium channel subunit alpha-1c. Chain: e, f. Fragment: c-terminal fragment: unp residues 1609-1682. Synonym: voltage-gated calcium channel subunit alpha cav1.2, calcium channel, l type, alpha-1 polypeptide, isoform 1, cardiac muscle.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: calm, calm1, calm2, calm3, calml2, cam, cam1, cam2, cam3, camb, camc, camiii. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: cacna1c, cach2, cacn2, cacnl1a1, cchl1a1.

Resolution:

2.10Å R-factor: 0.220 R-free: 0.269

Authors:

J.L.Fallon,F.A.Quiocho

Key ref:

J.L.Fallon et al. (2009). Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins. Proc Natl Acad Sci U S A, 106, 5135-5140. PubMed id: 19279214 DOI: 10.1073/pnas.0807487106

Date:

03-Feb-09 Release date: 03-Mar-09

Protein chain

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 75 a.a.

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 147 a.a.

Protein chain

Q13936  (CAC1C_HUMAN) -  Voltage-dependent L-type calcium channel subunit alpha-1C from Homo sapiens

Seq: 2221 a.a.

Struc: 68 a.a.*

Protein chain

Q13936  (CAC1C_HUMAN) -  Voltage-dependent L-type calcium channel subunit alpha-1C from Homo sapiens

Seq: 2221 a.a.

Struc: 45 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1073/pnas.0807487106

Proc Natl Acad Sci U S A 106:5135-5140 (2009)

PubMed id: 19279214

Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins.

J.L.Fallon, M.R.Baker, L.Xiong, R.E.Loy, G.Yang, R.T.Dirksen, S.L.Hamilton, F.A.Quiocho.

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.

Selected figure(s)

Figure 1.
Crystal structure of the C-terminal pre-IQ-IQ fragment from the Ca[V]1.2 α[1] subunit. CaM N-lobes/domains are tan; C-lobes light blue; Ca^2+ ions are gold spheres. Ca[V]1.2 fragments (I and II) are blue to orange rainbow starting from the N termini (marked with N); the IQ domain for fragment I is red. Loop regions, the IQ domain for fragment II, and the C-domain of CaM IV are not seen in the density and are modeled, by analogy with fragment I and CaM III, as thin light gray lines for reference. The N- and C-lobes of the extended form of CaMs I and II bridging the pre-IQ segments are separated by ≈15 Å, whereas those of CaM III bound to the IQ motif of Ca[V]I fragment make contacts. Figs. 1 and 2 were made with PyMOL (www.pymol.org).

Figure 3.
Schematic diagram of the residue contacts (<4.5 Å distance) of the Ca[v] I N-terminal region (T1609–1623; left column) with primarily the N-lobe of CaM I (residues in tan) and Ca[v] II C-terminal region (1633–1649; right column) with mainly the C-lobe of CaM I (residues in light blue). The total contacts of nonhydrogen atoms between Ca[v] I N-terminal region and CaM I N-lobe/C-lobe is ≈200 and that between Ca[v] II C-terminal region and CaM I C-lobe/N-lobe is ≈260. Similar contacts are made with CaM II lobes.

Figures were selected by an automated process.