3NFK

Crystal structure of the PTPN4 PDZ domain complexed with the C-terminus of a rabies virus G protein

3NFK の概要

• エントリーDOI: 10.2210/pdb3nfk/pdb
• 関連するPDBエントリー: 2CS5 2VPH 3NFL
• 分子名称: Tyrosine-protein phosphatase non-receptor type 4, Glycoprotein G, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pdz-pdz-binding site complex, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P29074; Virion membrane; Single-pass type I membrane protein (Potential): P03524
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 26526.06

構造登録者

Babault, N.,Cordier, F.,Lafage, M.,Cockburn, J.,Haouz, A.,Rey, F.A.,Delepierre, M.,Buc, H.,Lafon, M.,Wolff, N. (登録日: 2010-06-10, 公開日: 2011-08-24, 最終更新日: 2024-10-30)

主引用文献

Babault, N.,Cordier, F.,Lafage, M.,Cockburn, J.,Haouz, A.,Prehaud, C.,Rey, F.A.,Delepierre, M.,Buc, H.,Lafon, M.,Wolff, N.
Peptides Targeting the PDZ Domain of PTPN4 Are Efficient Inducers of Glioblastoma Cell Death.
Structure, 19:1518-1524, 2011

PubMed Abstract: PTPN4, a human tyrosine phosphatase, protects cells against apoptosis. This protection could be abrogated by targeting the PDZ domain of this phosphatase with a peptide mimicking the C-terminal sequence of the G protein of an attenuated rabies virus strain. Here, we demonstrate that glioblastoma death is triggered upon intracellular delivery of peptides, either from viral origin or from known endogenous ligands of PTPN4-PDZ, such as the C terminus sequence of the glutamate receptor subunit GluN2A. The killing efficiency of peptides closely reflects their affinities for the PTPN4-PDZ. The crystal structures of two PTPN4-PDZ/peptide complexes allow us to pinpoint the main structural determinants of binding and to synthesize a peptide of high affinity for PTPN4-PDZ enhancing markedly its cell death capacity. These results allow us to propose a potential mechanism for the efficiency of peptides and provide a target and a robust framework for the design of new pro-death compounds.

PubMed: 22000519
DOI: 10.1016/j.str.2011.07.007

実験手法

X-RAY DIFFRACTION (1.43 Å)