PDBsum entry 4ovn

Metal binding protein

PDB id: 4ovn

Contents

Protein chains

145 a.a.

146 a.a.

Ligands

SO4 ×5

PO4 ×2

Metals

_MG ×18

Waters ×62

PDB id:

4ovn

Name:

Metal binding protein

Title:

Voltage-gated sodium channel 1.5 (nav1.5) c-terminal domain in complex with calmodulin poised for activation

Structure:

Calmodulin. Chain: a, b, c, d, e. Synonym: cam. Engineered: yes. Sodium channel protein type 5 subunit alpha. Chain: f, g, h, i, j. Fragment: c-terminal domain (unp residue 1773-1929). Synonym: hh1,sodium channel protein cardiac muscle subunit alpha, sodium channel protein type v subunit alpha,voltage-gated sodium

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: scn5a. Expression_system_taxid: 562.

Resolution:

2.80Å R-factor: 0.215 R-free: 0.282

Authors:

S.B.Gabelli,M.A.Bianchet,A.Boto,J.Jakoncic,G.F.Tomaselli,L.M.Amzel

Key ref:

S.B.Gabelli et al. (2014). Regulation of the NaV1.5 cytoplasmic domain by calmodulin. Nat Commun, 5, 5126. PubMed id: 25370050 DOI: 10.1038/ncomms6126

Date:

10-Dec-13 Release date: 03-Dec-14

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 145 a.a.

Protein chains

Q14524  (SCN5A_HUMAN) -  Sodium channel protein type 5 subunit alpha from Homo sapiens

Seq: 2016 a.a.

Struc: 146 a.a.

DOI no: 10.1038/ncomms6126

Nat Commun 5:5126 (2014)

PubMed id: 25370050

Regulation of the NaV1.5 cytoplasmic domain by calmodulin.

S.B.Gabelli, A.Boto, V.H.Kuhns, M.A.Bianchet, F.Farinelli, S.Aripirala, J.Yoder, J.Jakoncic, G.F.Tomaselli, L.M.Amzel.

ABSTRACT

Voltage-gated sodium channels (Na(v)) underlie the rapid upstroke of action potentials in excitable tissues. Binding of channel-interactive proteins is essential for controlling fast and long-term inactivation. In the structure of the complex of the carboxy-terminal portion of Na(v)1.5 (CTNa(v)1.5) with calmodulin (CaM)-Mg(2+) reported here, both CaM lobes interact with the CTNa(v)1.5. On the basis of the differences between this structure and that of an inactivated complex, we propose that the structure reported here represents a non-inactivated state of the CTNa(v), that is, the state that is poised for activation. Electrophysiological characterization of mutants further supports the importance of the interactions identified in the structure. Isothermal titration calorimetry experiments show that CaM binds to CTNa(v)1.5 with high affinity. The results of this study provide unique insights into the physiological activation and the pathophysiology of Na(v) channels.