PDBsum entry 4k2o

Signaling protein

PDB id: 4k2o

Contents

Protein chain

232 a.a.

Waters ×103

PDB id:

4k2o

Name:

Signaling protein

Title:

The structure of a triple mutant of the tiam1 ph-cc-ex domain

Structure:

T-lymphoma invasion and metastasis-inducing protein 1. Chain: a. Fragment: ph-cc-ex domain (unp residues 429-702). Synonym: tiam-1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tiam1. Expressed in: escherichia coli. Expression_system_taxid: 1007065.

Resolution:

2.15Å R-factor: 0.178 R-free: 0.220

Authors:

M.Joshi,L.Gakhar,E.J.Fuentes

Key ref:

M.Joshi et al. (2013). High-resolution structure of the Tiam1 PHn-CC-Ex domain. Acta Crystallogr Sect F Struct Biol Cryst Commun, 69, 744-752. PubMed id: 23832200 DOI: 10.1107/S1744309113014206

Date:

09-Apr-13 Release date: 10-Jul-13

Protein chain

Q13009  (TIAM1_HUMAN) -  Rho guanine nucleotide exchange factor TIAM1 from Homo sapiens

Seq: 1591 a.a.

Struc: 232 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1107/S1744309113014206

Acta Crystallogr Sect F Struct Biol Cryst Commun 69:744-752 (2013)

PubMed id: 23832200

High-resolution structure of the Tiam1 PHn-CC-Ex domain.

M.Joshi, L.Gakhar, E.J.Fuentes.

ABSTRACT

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.