Structural features of the C8 antiviral peptide in a membrane-mimicking environment

• Published in: Biochimica et biophysica acta 2014-03, Vol.1838 (3), p.1010-1018
• Main Authors: Scrima, Mario, Di Marino, Sara, Grimaldi, Manuela, Campana, Federica, Vitiello, Giuseppe, Piotto, Stefano Piotto, D'Errico, Gerardino, D'Ursi, Anna Maria
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - chemistry; Cats; Cell Membrane - chemistry; Cellular Microenvironment; Circular Dichroism; Conformational analysis; Fluorescence; Glycoprotein; Humans; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; NMR; Peptide Fragments - chemistry; Protein Conformation; Spin Labels; Viral Envelope Proteins - chemistry; Viral fusion
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2013.12.010

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. [Display omitted] •Negatively charged membrane surface induces disordered C8 conformations.•Structures of FIV fusion peptides on membranes with different compositions•Water mediated interaction of C8 with negatively charged surface.•Hydrophobic binding mediates interaction of C8 with zwitterionic membrane model.