5XAX

Parallel homodimer structures of the extracellular domains of the voltage-gated sodium channel beta4 subunit explain its role in cell-cell adhesion

Summary for 5XAX

• Entry DOI: 10.2210/pdb5xax/pdb
• Related: 5XAW
• Descriptor: Sodium channel subunit beta-4, GLYCEROL (2 entities in total)
• Functional Keywords: ig, cell adhesion
• Biological source: Mus musculus (Mouse)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q7M729
• Total number of polymer chains: 2
• Total formula weight: 31675.46

Authors

Shimizu, H.,Yokoyama, S. (deposition date: 2017-03-15, release date: 2017-07-05, Last modification date: 2024-10-23)

Primary citation

Shimizu, H.,Tosaki, A.,Ohsawa, N.,Ishizuka-Katsura, Y.,Shoji, S.,Miyazaki, H.,Oyama, F.,Terada, T.,Shirouzu, M.,Sekine, S.I.,Nukina, N.,Yokoyama, S.
Parallel homodimer structures of the extracellular domains of the voltage-gated sodium channel beta 4 subunit explain its role in cell-cell adhesion
J. Biol. Chem., 292:13428-13440, 2017

PubMed Abstract: Voltage-gated sodium channels (VGSCs) are transmembrane proteins required for the generation of action potentials in excitable cells and essential for propagating electrical impulses along nerve cells. VGSCs are complexes of a pore-forming α subunit and auxiliary β subunits, designated as β1/β1B-β4 (encoded by respectively), which also function in cell-cell adhesion. We previously reported the structural basis for the homophilic interaction of the β4 subunit, which contributes to its adhesive function. Here, using crystallographic and biochemical analyses, we show that the β4 extracellular domains directly interact with each other in a parallel manner that involves an intermolecular disulfide bond between the unpaired Cys residues (Cys) in the loop connecting strands B and C and intermolecular hydrophobic and hydrogen-bonding interactions of the N-terminal segments (Ser-Val). Under reducing conditions, an N-terminally deleted β4 mutant exhibited decreased cell adhesion compared with the wild type, indicating that the β4 dimer contributes to the homophilic interaction of β4 in cell-cell adhesion. Furthermore, this mutant exhibited increased association with the α subunit, indicating that the dimerization of β4 affects α-β4 complex formation. These observations provide the structural basis for the parallel dimer formation of β4 in VGSCs and reveal its mechanism in cell-cell adhesion.

PubMed: 28655765
DOI: 10.1074/jbc.M117.786509

Experimental method

X-RAY DIFFRACTION (2.903 Å)