PDBsum entry 4jpz

Transport protein

PDB id: 4jpz

Contents

Protein chains

148 a.a.

142 a.a.

143 a.a.

Metals

_CA ×8

Waters ×31

PDB id:

4jpz

Name:

Transport protein

Title:

Voltage-gated sodium channel 1.2 c-terminal domain in complex with fgf13u and ca2+/calmodulin

Structure:

Fibroblast growth factor 13. Chain: a, e. Synonym: fgf-13, fibroblast growth factor homologous factor 2, fhf-2. Engineered: yes. Sodium channel protein type 2 subunit alpha. Chain: b, h. Synonym: hbsc ii, sodium channel protein brain ii subunit alpha, sodium channel protein type ii subunit alpha, voltage-gated sodium channel subunit alpha nav1.2.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgf13, fhf2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: scn2a, nac2, scn2a1, scn2a2. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, calml2, cam3, camc, camiii.

Resolution:

3.02Å R-factor: 0.215 R-free: 0.246

Authors:

C.Wang,B.C.Chung,H.Yan,H.G.Wang,S.Y.Lee,G.S.Pitt

Key ref:

C.Wang et al. (2014). Structural analyses of Ca²⁺/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation. Nat Commun, 5, 4896. PubMed id: 25232683 DOI: 10.1038/ncomms5896

Date:

19-Mar-13 Release date: 16-Apr-14

Protein chains

Q92913  (FGF13_HUMAN) -  Fibroblast growth factor 13 from Homo sapiens

Seq: 245 a.a.

Struc: 148 a.a.

Protein chains

Q99250  (SCN2A_HUMAN) -  Sodium channel protein type 2 subunit alpha from Homo sapiens

Seq: 2005 a.a.

Struc: 142 a.a.

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 143 a.a.

DOI no: 10.1038/ncomms5896

Nat Commun 5:4896 (2014)

PubMed id: 25232683

Structural analyses of Ca²⁺/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation.

C.Wang, B.C.Chung, H.Yan, H.G.Wang, S.Y.Lee, G.S.Pitt.

ABSTRACT

Ca(2+) regulates voltage-gated Na(+) (NaV) channels, and perturbed Ca(2+) regulation of NaV function is associated with epilepsy syndromes, autism and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of structural information and competing models for how Ca(2+) affects NaV channel function. Here we report the crystal structures of two ternary complexes of a human NaV cytosolic C-terminal domain (CTD), a fibroblast growth factor homologous factor and Ca(2+)/calmodulin (Ca(2+)/CaM). These structures rule out direct binding of Ca(2+) to the NaV CTD and uncover new contacts between CaM and the NaV CTD. Probing these new contacts with biochemical and functional experiments allows us to propose a mechanism by which Ca(2+) could regulate NaV channels. Further, our model provides hints towards understanding the molecular basis of the neurologic disorders and cardiac arrhythmias caused by NaV channel mutations.