The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module

Shin Ichi Terawaki, Ken Kitano, Tomoyuki Mori, Yan Zhai, Yoshiki Higuchi, Norimichi Itoh, Takashi Watanabe, Kozo Kaibuchi, Toshio Hakoshima

研究成果: Article査読

27 被引用数 (Scopus)

抄録

Tiam1 and Tiam2 (Tiam1/2) are guanine nucleotide-ex-change factors that possess the PH-CC-Ex (pleckstrin homology, coiled coil and extra) region that mediates binding to plasma membranes and signalling proteins in the activation of Rac GTPases. Crystal structures of the PH-CC-Ex regions revealed a single globular domain, PHCCEx domain, comprising a conventional PH subdomain associated with an antiparallel coiled coil of CC subdomain and a novel three-helical globular Ex subdomain. The PH subdomain resembles the β-spectrin PH domain, suggesting non-canonical phosphatidylinositol binding. Mutational and binding studies indicated that CC and Ex subdomains form a positively charged surface for protein binding. We identified two unique acidic sequence motifs in Tiam1/2-interacting proteins for binding to PHCCEx domain, Motif-I in CD44 and ephrinB's and the NMDA receptor, and Motif-II in Par3 and JIP2. Our results suggest the molecular basis by which the Tiam1/2 PHCCEx domain facilitates dual binding to membranes and signalling proteins.

本文言語English
ページ(範囲)236-250
ページ数15
ジャーナルEMBO Journal
29
1
DOI
出版ステータスPublished - 06-01-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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