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

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)236-250
Number of pages15
JournalEMBO Journal
Issue number1
Publication statusPublished - 06-01-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology


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