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4k2p

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The Structure of a Quintuple Mutant of the Tiam1 PH-CC-Ex Domain

Structural highlights

4k2p is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.98Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TIAM1_HUMAN Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates RAC1, CDC42, and to a lesser extent RHOA.

Publication Abstract from PubMed

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 approximately 30 microM. Moreover, the structures of two variants of the Tiam1 PHn-CC-Ex domain were solved at resolutions of 1.98 and 2.15 A, 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.

High-resolution structure of the Tiam1 PHn-CC-Ex domain.,Joshi M, Gakhar L, Fuentes EJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jul;69(Pt 7):744-52. doi: , 10.1107/S1744309113014206. Epub 2013 Jun 27. PMID:23832200^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Joshi M, Gakhar L, Fuentes EJ. High-resolution structure of the Tiam1 PHn-CC-Ex domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jul;69(Pt 7):744-52. doi: , 10.1107/S1744309113014206. Epub 2013 Jun 27. PMID:23832200 doi:10.1107/S1744309113014206