3nfk

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

spinqualitylabelsall models 3nfk, resolution 1.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3nfk is a 4 chain structure with sequence from Homo sapiens and Rabies lyssavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.43Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PTN4_HUMAN May act at junctions between the membrane and the cytoskeleton. Publication Abstract from PubMed 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. Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death.,Babault N, Cordier F, Lafage M, Cockburn J, Haouz A, Prehaud C, Rey FA, Delepierre M, Buc H, Lafon M, Wolff N Structure. 2011 Oct 12;19(10):1518-24. PMID:22000519 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine phosphatase 3D structures

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