Structure-based site-directed photo-crosslinking analyses of multimeric cell-adhesive interactions of voltage-gated sodium channel β subunits

Hideaki Shimizu, Haruko Miyazaki, Noboru Ohsawa, Shisako Shoji, Yoshiko Ishizuka-Katsura, Asako Tosaki, Fumitaka Oyama, Takaho Terada, Kensaku Sakamoto, Mikako Shirouzu, Shun Ichi Sekine, Nobuyuki Nukina, Shigeyuki Yokoyama

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The β1, β2, and β4 subunits of voltage-gated sodium channels reportedly function as cell adhesion molecules. The present crystallographic analysis of the β4 extracellular domain revealed an antiparallel arrangement of the β4 molecules in the crystal lattice. The interface between the two antiparallel β4 molecules is asymmetric, and results in a multimeric assembly. Structure-based mutagenesis and site-directed photo-crosslinking analyses of the β4-mediated cell-cell adhesion revealed that the interface between the antiparallel β4 molecules corresponds to that in the trans homophilic interaction for the multimeric assembly of β4 in cell-cell adhesion. This trans interaction mode is also employed in the β1-mediated cell-cell adhesion. Moreover, the β1 gene mutations associated with generalized epilepsy with febrile seizures plus (GEFS+) impaired the β1-mediated cell-cell adhesion, which should underlie the GEFS+ pathogenesis. Thus, the structural basis for the β-subunit-mediated cell-cell adhesion has been established.

Original languageEnglish
Article number26618
JournalScientific reports
Volume6
DOIs
Publication statusPublished - May 24 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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