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PDBsum entry 3a8p
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Signaling protein
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PDB id
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3a8p
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References listed in PDB file
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Key reference
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Title
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The phccex domain of tiam1/2 is a novel protein- And membrane-Binding module.
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Authors
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S.Terawaki,
K.Kitano,
T.Mori,
Y.Zhai,
Y.Higuchi,
N.Itoh,
T.Watanabe,
K.Kaibuchi,
T.Hakoshima.
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Ref.
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Embo J, 2010,
29,
236-250.
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PubMed id
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Abstract
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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.
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