PDBsum entry 2m5e

Calcium-binding protein/metal transport

PDB id: 2m5e

Contents

Protein chains

73 a.a.

27 a.a.

Metals

_CA ×2

PDB id:

2m5e

Name:

Calcium-binding protein/metal transport

Title:

Structure of thE C-domain of calcium-saturated calmodulin bound to the iq motif of nav1.2

Structure:

Calmodulin. Chain: a. Fragment: unp residues 77-149. Synonym: cam. Engineered: yes. Sodium channel protein type 2 subunit alpha. Chain: b. Fragment: unp residues 1901-1927. Synonym: sodium channel protein brain ii subunit alpha, sodium

Source:

Paramecium tetraurelia. Organism_taxid: 5888. Strain: d4-2. Gene: cam, gspatt00015825001. Expressed in: escherichia coli. Expression_system_taxid: 469008. Rattus norvegicus. Rat. Organism_taxid: 10116.

NMR struc:

21 models

Authors:

C.A.Fowler,M.D.Feldkamp,L.Yu,M.A.Shea

Key ref:

L.Hovey et al. (2017). Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2. Biophys Chem, 224, 1. PubMed id: 28343066 DOI: 10.1016/j.bpc.2017.02.006

Date:

21-Feb-13 Release date: 23-Jul-14

Protein chain

P07463  (CALM_PARTE) -  Calmodulin from Paramecium tetraurelia

Seq: 149 a.a.

Struc: 73 a.a.

Protein chain

P04775  (SCN2A_RAT) -  Sodium channel protein type 2 subunit alpha from Rattus norvegicus

Seq: 2005 a.a.

Struc: 27 a.a.

DOI no: 10.1016/j.bpc.2017.02.006

Biophys Chem 224:1 (2017)

PubMed id: 28343066

Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2.

L.Hovey, C.A.Fowler, R.Mahling, Z.Lin, M.S.Miller, D.C.Marx, J.B.Yoder, E.H.Kim, K.M.Tefft, B.C.Waite, M.D.Feldkamp, L.Yu, M.A.Shea.

ABSTRACT

Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca(2+))4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca(2+))4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1.2IQp) exclusively made contacts with C-domain residues of CaM (CaMC). To understand how calcium triggers conformational change at the CaM-IQ interface, we determined a solution structure (2M5E.pdb) of (Ca(2+))2-CaMC bound to NaV1.2IQp. The polarity of (Ca(2+))2-CaMC relative to the IQ motif was opposite to that seen in apo CaMC-Nav1.2IQp (2KXW), revealing that CaMC recognizes nested, anti-parallel sites in Nav1.2IQp. Reversal of CaM may require transient release from the IQ motif during calcium binding, and facilitate a re-orientation of CaMN allowing interactions with non-IQ NaV1.2 residues or auxiliary regulatory proteins interacting in the vicinity of the IQ motif.