NR AEHK
AU Gabus,C.; Derrington,E.A.; Leblanc,P.; Chnaiderman,J.; Dormont,D.; Swietnicki,W.; Morillas,M.; Surewicz,W.K.; Marc,D.; Nandi,P.; Darlix,J.L.
TI The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1
QU The Journal of Biological Chemistry 2001 Jun 1; 276(22): 19301-9
PT journal article
AB Transmissible spongiform encephalopathies are fatal neurodegenerative diseases associated with the accumulation of a protease-resistant form of the prion protein (PrP). Although PrP is conserved in vertebrates, its function remains to be identified. In vitro PrP binds large nucleic acids causing the formation of nucleoprotein complexes resembling human immunodeficiency virus type 1 (HIV-1) nucleocapsid-RNA complexes and in vivo MuLV replication accelerates the scrapie infectious process, suggesting possible interactions between retroviruses and PrP. Retroviruses, including HIV-1 encode a major nucleic acid binding protein (NC protein) found within the virus where 2000 NC protein molecules coat the dimeric genome. NC is required in virus assembly and infection to chaperone RNA dimerization and packaging and in proviral DNA synthesis by reverse transcriptase (RT). In HIV-1, 5'-leader RNA/NC interactions appear to control these viral processes. This prompted us to compare and contrast the interactions of human and ovine PrP and HIV-1 NCp7 with HIV-1 5'-leader RNA. Results show that PrP has properties characteristic of NCp7 with respect to viral RNA dimerization and proviral DNA synthesis by RT. The NC-like properties of huPrP map to the N-terminal region of huPrP. Interestingly, PrP localizes in the membrane and cytoplasm of PrP-expressing cells. These findings suggest that PrP is a multifunctional protein possibly participating in nucleic acid metabolism.
MH 5' Untranslated Regions/metabolism; Amino Acid Sequence; Animal; Base Sequence; Binding Sites; Capsid/*chemistry/physiology; Cattle; Cell Line; Cell Membrane/metabolism; Cytoplasm/metabolism; DNA/metabolism; DNA, Complementary/metabolism; Dimerization; Escherichia coli/metabolism; Gene Products, gag/*chemistry/physiology; HIV-1/metabolism; Human; Immunohistochemistry; Models, Biological; Models, Genetic; Molecular Chaperones/metabolism; Molecular Sequence Data; Nucleoproteins/metabolism; Plasmids/metabolism; Prions/*chemistry/*physiology; Protein Binding; RNA/*metabolism; RNA-Directed DNA Polymerase/metabolism; Recombinant Proteins/metabolism; Retroviridae/genetics; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic; Transfection
AD
Caroline Gabus, Edmund Derrington, Pascal Leblanc, Jonas Chnaiderman, Jean-Luc Darlix, LaboRetro, Unité de Virologie Humaine INSERM-Ecole Normale Superieure de Lyon (ENS) 412, ENS de Lyon, 46 Allée d'Italie, Lyon 69364, France
Dominique Dormont, Département de Recherche Médicale, Commissariat à l'Energie Anatomique, BP6, Fontenay-aux-Roses 92265, France
Wieslaw Swietnicki, Manuel Morillas, Witold K. Surewicz, Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106
Daniel Marci, Pradip Nandii, Institut National de la Recherche Agronomique, Centre de Recherches de Tours, Nouzilly 37380, France
SP englisch
PO USA