首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death
Authors:Babault Nicolas  Cordier Florence  Lafage Mireille  Cockburn Joseph  Haouz Ahmed  Prehaud Christophe  Rey Félix A  Delepierre Muriel  Buc Henri  Lafon Monique  Wolff Nicolas
Institution:Unité de Résonance Magnétique Nucléaire des Biomolécules, Département de Biologie Structurale et Chimie, Institut Pasteur, F-75724 Paris, France.
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.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号