Abstract
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 language | English |
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Pages (from-to) | 236-250 |
Number of pages | 15 |
Journal | EMBO Journal |
Volume | 29 |
Issue number | 1 |
DOIs | |
Publication status | Published - 06-01-2010 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- General Neuroscience
- Molecular Biology
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology