title: Structural features of the C8 antiviral peptide in a membrane-mimicking environment.
abstract: C8, a short peptide characterized by three regularly spaced Trp residues, belongs to the membrane-proximal external functional domains of the feline immunodeficiency virus coat protein gp36. It elicits antiviral activity as a result of blocking cell entry and exhibits membranotropic and fusogenic activities. Membrane-proximal external functional domains of virus coat proteins are potential targets in the development of new anti-HIV drugs that overcome the limitations of the current anti-retroviral therapy. In the present work, we studied the conformation of C8 and its interaction with micellar surfaces using circular dichroism, nuclear magnetic resonance and fluorescence spectroscopy. The experimental data were integrated by molecular dynamics simulations in a micelle-water system. Our data provide insight into the environmental conditions related to the presence of the fusogenic peptide C8 on zwitterionic or negatively charged membranes. The membrane charge modulates the conformational features of C8. A zwitterionic membrane surface induces C8 to assume canonical secondary structures, with hydrophobic interactions between the Trp residues and the phospholipid chains of the micelles. A negatively charged membrane surface favors disordered C8 conformations and unspecific superficial interactions, resulting in membrane destabilization.
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scrima
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Marino
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Campana
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Stefano Piotto
authors.initials: SP
authors.lastname: Piotto
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Naples, Italy.
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy. Electronic address: dursi@unisa.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry*; D002415:Cats; D002462:Cell Membrane / Q000737:chemistry*; D060833:Cellular Microenvironment; D002942:Circular Dichroism; D005453:Fluorescence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D013113:Spin Labels; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D010446:Peptide Fragments; D013113:Spin Labels; D014759:Viral Envelope Proteins
keywords: Conformational analysis; Glycoprotein; NMR; Viral fusion