title: Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site 3: role of site-specific mutations.
abstract: Proteolytic processing of HIV gp160 to produce gp120 and gp41 is performed by PC enzymes. This process is a prerequisite for the virus infectivity, since both gp120 and gp41 participate in the virus HIV-1 entry mechanism. The structure of the gp120/gp41 junction remains to be elucidated, and the structural features required for molecular recognition between HIV-1 gp160 and proteolytic enzymes have not been clarified. Furin is the best PC candidate for the gp160 proteolytic processing known to date. In previous studies on model peptides, we have shown the relevance of an N-terminal helix for the proper recognition of the gp160 processing site by furin. Here we analyze the effect of point mutations in peptides lacking a regular N-terminal helix. To this end, we present the structure-activity characterization of three peptide analogues of the HIV gp160 processing site that all present mutations in proline at positions P3 and/or P2', while sharing the same N-terminal sequence, containing helix-breaking D-amino acids. Conformational analysis of the peptides was carried out in solution by NMR techniques, and furin's efficiency in cleaving them was measured. Structural findings are presented and discussed in relation to the different exhibited activity.
authors.affiliation: Dipartimento di Chimica, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 80126 Napoli, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Falcigno
authors.forename: Romina
authors.initials: R
authors.lastname: Oliva
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Auria
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Maletta
authors.forename: Monica
authors.initials: M
authors.lastname: Dettin
authors.forename: Antonella
authors.initials: A
authors.lastname: Pasquato
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Bello
authors.forename: Livio
authors.initials: L
authors.lastname: Paolillo
mesh_terms: D020134:Catalytic Domain; D045683:Furin / Q000494:pharmacology; D019302:HIV Envelope Protein gp160 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry; D017354:Point Mutation; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation / Q000187:drug effects
chemical_list: D019302:HIV Envelope Protein gp160; D010446:Peptide Fragments; D011392:Proline; D045683:Furin