title: Proteolytic cleavage of wild type and mutants of the F protein of human parainfluenza virus type 3 by two subtilisin-like endoproteases, furin and Kex2.
abstract: The fusion (F) protein of human parainfluenza virus type 3 contains the tribasic cleavage site R-T-K-R, which was altered by site-directed mutagenesis. Wild-type F protein and various mutants were expressed by recombinant vaccinia viruses. The endogenous endoprotease present in CV-1 cells cleaves F variants containing the furin recognition motif R-X-K/R-R but not variants containing the dibasic site K-R or a single R at the cleavage site. A similar cleavage pattern was obtained when the subtilisin-like endoproteases Kex2 and furin were coexpressed with the wild type and mutants of the F protein. Peptidylchloromethylketone inhibitors mimicking basic cleavage sites prevent cleavage of the precursor Fo by the endogenous protease only when the furin-specific motif is present in the peptidyl portion. The data support the concept that furin is a cellular protease responsible for the activation of the F protein of human parainfluenza virus type 3.
authors.affiliation: Institut für Virologie, Philipps-Universität Marburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Ortmann
authors.forename: M
authors.initials: M
authors.lastname: Ohuchi
authors.forename: H
authors.initials: H
authors.lastname: Angliker
authors.forename: E
authors.initials: E
authors.lastname: Shaw
authors.forename: W
authors.initials: W
authors.lastname: Garten
authors.forename: H D
authors.initials: HD
authors.lastname: Klenk
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D045683:Furin; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010224:Parainfluenza Virus 3, Human / Q000378:metabolism*; D043484:Proprotein Convertases; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013381:Subtilisins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014760:Viral Fusion Proteins; D043484:Proprotein Convertases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae; D045683:Furin