PDBsum entry 4l1d

Membrane protein

PDB id: 4l1d

Contents

Protein chains

113 a.a.

Waters ×117

PDB id:

4l1d

Name:

Membrane protein

Title:

Voltage-gated sodium channel beta3 subunit ig domain

Structure:

Sodium channel subunit beta-3. Chain: a, b, c. Fragment: ig domain, unp residues 25-145. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kiaa1158, scn3b. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293f.

Resolution:

2.50Å R-factor: 0.205 R-free: 0.238

Authors:

S.Namadurai,M.Weimhofer,R.Rajappa,K.Stott,J.Klingauf,D.Y.Chirgadze, A.P.Jackson

Key ref:

S.Namadurai et al. (2014). Crystal structure and molecular imaging of the Nav channel β3 subunit indicates a trimeric assembly. J Biol Chem, 289, 10797-10811. PubMed id: 24567321 DOI: 10.1074/jbc.M113.527994

Date:

03-Jun-13 Release date: 05-Mar-14

Protein chains

Q9NY72  (SCN3B_HUMAN) -  Sodium channel regulatory subunit beta-3 from Homo sapiens

Seq: 215 a.a.

Struc: 113 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1074/jbc.M113.527994

J Biol Chem 289:10797-10811 (2014)

PubMed id: 24567321

Crystal structure and molecular imaging of the Nav channel β3 subunit indicates a trimeric assembly.

S.Namadurai, D.Balasuriya, R.Rajappa, M.Wiemhöfer, K.Stott, J.Klingauf, J.M.Edwardson, D.Y.Chirgadze, A.P.Jackson.

ABSTRACT

The vertebrate sodium (Nav) channel is composed of an ion-conducting α subunit and associated β subunits. Here, we report the crystal structure of the human β3 subunit immunoglobulin (Ig) domain, a functionally important component of Nav channels in neurons and cardiomyocytes. Surprisingly, we found that the β3 subunit Ig domain assembles as a trimer in the crystal asymmetric unit. Analytical ultracentrifugation confirmed the presence of Ig domain monomers, dimers, and trimers in free solution, and atomic force microscopy imaging also detected full-length β3 subunit monomers, dimers, and trimers. Mutation of a cysteine residue critical for maintaining the trimer interface destabilized both dimers and trimers. Using fluorescence photoactivated localization microscopy, we detected full-length β3 subunit trimers on the plasma membrane of transfected HEK293 cells. We further show that β3 subunits can bind to more than one site on the Nav 1.5 α subunit and induce the formation of α subunit oligomers, including trimers. Our results suggest a new and unexpected role for the β3 subunits in Nav channel cross-linking and provide new structural insights into some pathological Nav channel mutations.