3NFK

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

Summary for 3NFK

• Entry DOI: 10.2210/pdb3nfk/pdb
• Related: 2CS5 2VPH 3NFL
• Descriptor: Tyrosine-protein phosphatase non-receptor type 4, Glycoprotein G, GLYCEROL, ... (4 entities in total)
• Functional Keywords: pdz-pdz-binding site complex, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P29074; Virion membrane; Single-pass type I membrane protein (Potential): P03524
• Total number of polymer chains: 4
• Total formula weight: 26526.06

Authors

Babault, N.,Cordier, F.,Lafage, M.,Cockburn, J.,Haouz, A.,Rey, F.A.,Delepierre, M.,Buc, H.,Lafon, M.,Wolff, N. (deposition date: 2010-06-10, release date: 2011-08-24, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.43 Å)