Structural investigation of the HIV-1 envelopeglycoprotein gp160 cleavage site 3: role ofsite-specific mutations
| Autor: | Carlo Di Bello, Lucia Falcigno, Monica Dettin, Livio Paolillo, Massimiliano Maletta, Romina Oliva, Antonella Pasquato, Gabriella D'Auria |
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| Přispěvatelé: | Falcigno, Lucia, R., Oliva, D'Auria, Gabriella, M., Maletta, M., Dettin, A., Pasquato, C., di Bello, L., Paolillo |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Proline
Protein Conformation viruses Peptide Gp41 Biochemistry HIV Envelope Protein gp160 Molecular recognition Catalytic Domain Humans Point Mutation Molecular Biology Furin chemistry.chemical_classification biology Point mutation Organic Chemistry Proteolytic enzymes virus diseases Peptide Fragments NMR Enzyme chemistry gp160 Mutagenesis Site-Directed biology.protein HIV-1 Molecular Medicine Glycoprotein Peptides furin |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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