Structural highlights
Function
[PTN4_HUMAN] May act at junctions between the membrane and the cytoskeleton. [VGLG_RABVE] Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein G and thereby facilitate rabies virus entry into cells.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Babault N, Cordier F, Lafage M, Cockburn J, Haouz A, Prehaud C, Rey FA, Delepierre M, Buc H, Lafon M, Wolff N. Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death. Structure. 2011 Oct 12;19(10):1518-24. PMID:22000519 doi:10.1016/j.str.2011.07.007
