4GVC

Crystal Structure of T-cell Lymphoma Invasion and Metastasis-1 PDZ in complex with phosphorylated Syndecan1 Peptide

4GVC の概要

• エントリーDOI: 10.2210/pdb4gvc/pdb
• 関連するPDBエントリー: 3KZD 3KZE 4GVD
• 分子名称: T-lymphoma invasion and metastasis-inducing protein 1, Syndecan-1, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: phosphorylation, peptide conformational change, new binding pocket, scaffold signaling protein for cell adhesion and cell junction, syndecan1 p1 tyr phosphorylation, sydencan1 n-terminal thr dansylation, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell junction: Q13009; Membrane; Single-pass type I membrane protein: P18827
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11595.70

構造登録者

Liu, X.,Shepherd, T.R.,Murray, A.M.,Xu, Z.,Fuentes, E.J. (登録日: 2012-08-30, 公開日: 2013-03-13, 最終更新日: 2024-11-27)

主引用文献

Liu, X.,Shepherd, T.R.,Murray, A.M.,Xu, Z.,Fuentes, E.J.
The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.
Structure, 21:342-354, 2013

PubMed 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.

PubMed: 23395182
DOI: 10.1016/j.str.2013.01.004

実験手法

X-RAY DIFFRACTION (1.54 Å)