title: Deletion of sequences upstream of the proteinase improves the proteolytic processing of human immunodeficiency virus type 1.
abstract: Human immunodeficiency virus type 1 expresses structural proteins and replicative enzymes within gag and gag-pol precursor polyproteins. Specific proteolytic processing of the precursors by the viral proteinase is essential for maturation of infectious viral particles. We have studied the activity of proteinase in its immature form, as part of a gag-pol fusion protein, in an in vitro expression system. We found that deletion of p6*, the region in pol upstream of proteinase, resulted in improved processing of the precursor. A modified proteinase is released, but it functions less efficiently than wild type. Improved autoprocessing correlates with increased accessibility of the active site region in the polyprotein carrying the p6* deletion. Our results suggest that p6* is involved in the regulation of proteinase activation, perhaps as a region limiting the interaction of the active site and substrate binding domain with the remainder of the polyprotein. Release of p6* inhibition may be an activation step necessary for infectious particle maturation.
authors.affiliation: Department of Microbiology, State University of New York, Stony Brook 11794.
authors.forename: K
authors.initials: K
authors.lastname: Partin
authors.forename: G
authors.initials: G
authors.lastname: Zybarth
authors.forename: L
authors.initials: L
authors.lastname: Ehrlich
authors.forename: M
authors.initials: M
authors.lastname: DeCrombrugghe
authors.forename: E
authors.initials: E
authors.lastname: Wimmer
authors.forename: C
authors.initials: C
authors.lastname: Carter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002474:Cell-Free System; D002872:Chromosome Deletion; D005814:Genes, Viral; D016333:HIV Protease / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics; D008969:Molecular Sequence Data; D010435:Pepsinogens / Q000235:genetics; D010957:Plasmids; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D010435:Pepsinogens; D016333:HIV Protease