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開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Structural basis for the trans- and cis-interactions of the voltage-gated sodium channel β subunits

  • P3-056
  • 清水 英明 / Hideaki Shimizu:1,2 白水 美香子 / Mikako Shirouzu:1,2 貫名 信行 / Nobuyuki Nukina:4 関根 俊一 / Shun-ichi Sekine:1,2 横山 茂之 / Shigeyuki Yokoyama:1,3 
  • 1:理化学研究所 ライフサイエンス技術基盤研究センター / RIKEN Center for Life Science Technologies 2:理化学研究所 生命分子システム基盤研究領域 / RIKEN Systems and Structural Biology Center 3:理化学研究所 横山構造生物学研究室 / RIKEN Structural Biology Laboratory 4:順天堂大学 / Juntendo University School of Medicine 

Voltage-gated sodium channel β subunits are multifunctional molecules that associate with the α subunits to modulate channel functions, and also participate in cell-cell adhesion. Mutations in the β subunit cause human epilepsies, such as generalized epilepsy with febrile seizures plus (GEFS+). Our previous X-ray crystallography and cell biology analyses demonstrated that the β4 extracellular domain forms a strand-exchanged parallel dimer, as a cis-homophilic interaction. Moreover, the parallel dimers interacted with each other in an antiparallel arrangement, and formed layers in the crystal. We hypothesized that this arrangement may represent a view of the trans-homophilic interaction in cell-cell adhesion.
To test this hypothesis, we performed site-directed mutagenesis studies of the β4 extracellular domain. The deletion of strand A disrupted both the parallel dimer formation and the cell-cell adhesion by the β4 subunit. Another β4 mutant, which forms a displaced parallel dimer, also exhibited impaired cell-cell adhesion. These findings suggested a novel mechanism of β subunit extracellular domain interactions, in which the parallel dimer formation facilitates the trans-homophilic interaction in cell-cell adhesion.

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