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Poster

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

電位依存性ナトリウムチャネルのホモフィリック相互作用における構造的基盤
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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