| First Author | Terawaki S | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 1 | Pages | 236-50 |
| PubMed ID | 19893486 | Mgi Jnum | J:156410 |
| Mgi Id | MGI:4420511 | Doi | 10.1038/emboj.2009.323 |
| Citation | Terawaki S, et al. (2010) The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module. EMBO J 29(1):236-50 |
| abstractText | Tiam1 and Tiam2 (Tiam1/2) are guanine nucleotide-exchange 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 beta-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. |
