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PDBsum entry 4k2o
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Signaling protein
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PDB id
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4k2o
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References listed in PDB file
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Key reference
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Title
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High-Resolution structure of the tiam1 phn-Cc-Ex domain.
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Authors
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M.Joshi,
L.Gakhar,
E.J.Fuentes.
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Ref.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 2013,
69,
744-752.
[DOI no: ]
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PubMed id
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Abstract
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The T-lymphoma and metastasis gene 1 (TIAM1) encodes a guanine
nucleotide-exchange factor protein (Tiam1) that is specific for the Rho-family
GTPase Rac1 and is important for cell polarity, migration and adhesion. Tiam1 is
a large multi-domain protein that contains several protein-protein binding
domains that are important for regulating cellular function. The PHn-CC-Ex
domain is critical for plasma-membrane association and interactions with
protein-scaffold proteins (e.g. Par3b, spinophilin, IRSp53 and JIP2) that direct
Tiam1-Rac1 signaling specificity. It was determined that the coiled-coil domain
of Par3b binds the PHn-CC-Ex domain with a dissociation constant of ≈ 30 µM.
Moreover, the structures of two variants of the Tiam1 PHn-CC-Ex domain were
solved at resolutions of 1.98 and 2.15 Å, respectively. The structures
indicate that the PHn, CC and Ex regions form independent subdomains that
together provide an integrated platform for binding partner proteins.
Small-angle X-ray scattering (SAXS) data indicate that the Tiam1 PHn-CC-Ex
domain is monomeric in solution and that the solution and crystal structures are
very similar. Together, these data provide the foundation necessary to elucidate
the structural mechanism of the PHn-CC-Ex/scaffold interactions that are
critical for Tiam1-Rac1 signaling specificity.
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