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

References listed in PDB file

Key reference

• Title: The structure of the tiam1 pdz domain/ phospho-Syndecan1 complex reveals a ligand conformation that modulates protein dynamics.
• Authors: X.Liu, T.R.Shepherd, A.M.Murray, Z.Xu, E.J.Fuentes.
• Ref.: Structure, 2013, 21, 342-354. [DOI no: 10.1016/j.str.2013.01.004]
• PubMed id: 23395182

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.