PDBsum entry 4gvc

Signaling protein

PDB id: 4gvc

Contents

Protein chain

94 a.a.

Ligands

THR-LYS-GLN-GLU-GLU-PHE-PTR-ALA

ANS

Metals

_CL ×2

_NA

Waters ×96

PDB id:

4gvc

Name:

Signaling protein

Title:

Crystal structure of t-cell lymphoma invasion and metastasis-1 pdz in complex with phosphorylated syndecan1 peptide

Structure:

T-lymphoma invasion and metastasis-inducing protein 1. Chain: a. Fragment: pdz domain (unp residues 841-930). Synonym: tiam-1. Engineered: yes. Syndecan-1. Chain: b. Fragment: unp residues 303-310. Synonym: synd1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: human. Gene: tiam1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.54Å R-factor: 0.167 R-free: 0.200

Authors:

X.Liu,T.R.Shepherd,A.M.Murray,Z.Xu,E.J.Fuentes

Key ref:

X.Liu et al. (2013). The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics. Structure, 21, 342-354. PubMed id: 23395182 DOI: 10.1016/j.str.2013.01.004

Date:

30-Aug-12 Release date: 13-Mar-13

Protein chain

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

Seq: 1591 a.a.

Struc: 94 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/j.str.2013.01.004

Structure 21:342-354 (2013)

PubMed id: 23395182

The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.

X.Liu, T.R.Shepherd, A.M.Murray, Z.Xu, E.J.Fuentes.

ABSTRACT

PDZ (PSD-95/Dlg/ZO-1) domains are protein-protein interaction modules often regulated by ligand phosphorylation. Here, we investigated the specificity, structure, and dynamics of Tiam1 PDZ domain/ligand interactions. We show that the PDZ domain specifically binds syndecan1 (SDC1), phosphorylated SDC1 (pSDC1), and SDC3 but not other syndecan isoforms. The crystal structure of the PDZ/SDC1 complex indicates that syndecan affinity is derived from amino acids beyond the four C-terminal residues. Remarkably, the crystal structure of the PDZ/pSDC1 complex reveals a binding pocket that accommodates the phosphoryl group. Methyl relaxation experiments of PDZ/SCD1 and PDZ/pSDC1 complexes reveal that PDZ-phosphoryl interactions dampen dynamic motions in a distal region of the PDZ domain by decoupling them from the ligand-binding site. Our data are consistent with a selection model by which specificity and phosphorylation regulate PDZ/syndecan interactions and signaling events. Importantly, our relaxation data demonstrate that PDZ/phospho-ligand interactions regulate protein dynamics and their coupling to distal sites.