title: A catalogue of putative HIV-1 protease host cell substrates.
abstract: Processing of human immunodeficiency virus (HIV) proteins by the HIV-1 protease is essential for HIV infectivity. In addition, several studies have revealed cleavage of human proteins by this viral protease during infection; however, no large-scale HIV-1 protease degradomics study has yet been performed. To identify putative host substrates in an unbiased manner and on a proteome-wide scale, we used positional proteomics to identify peptides reporting protein processing by the HIV-1 protease, and a catalogue of over 120 cellular HIV-1 protease substrates processed in vitro was generated. This catalogue includes previously reported substrates as well as recently described interaction partners of HIV-1 proteins. Cleavage site alignments revealed a specificity profile in good correlation with previous studies, even though the ELLE consensus motif was not cleaved efficiently when incorporated into peptide substrates due to subsite cooperativity. Our results are further discussed in the context of HIV-1 infection and the complex substrate recognition by the viral protease.
authors.affiliation: Department of Medical Protein Research and Biochemistry, VIB, B-9000 Ghent, Belgium.
authors.forename: Francis
authors.initials: F
authors.lastname: Impens
authors.forename: Evy
authors.initials: E
authors.lastname: Timmerman
authors.forename: An
authors.initials: A
authors.lastname: Staes
authors.forename: Kathleen
authors.initials: K
authors.lastname: Moens
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ariën
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Joël
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
mesh_terms: D000595:Amino Acid Sequence; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D019169:Jurkat Cells; D013379:Substrate Specificity
chemical_list: D016333:HIV Protease