Biological membranes represent a physical barrier that most viruses have to cross for replication. While enveloped viruses cross membranes through a well-characterized membrane fusion mechanism, non-enveloped viruses, such as rotaviruses, require the destabilization of the host cell membrane by processes that are still poorly understood. We have identified, in the C-terminal region of the rotavirus glycoprotein VP7, a peptide that was predicted to contain a membrane domain and to fold into an amphipathic α-helix. Its structure was confirmed by circular dichroism in media mimicking the hydrophobic environment of the membrane at both acidic and neutral pHs. The helical folding of the peptide was corroborated by ATR-FTIR spectroscopy, which suggested a transmembrane orientation of the peptide. The interaction of this peptide with artificial membranes and its affinity were assessed by plasmon waveguide resonance. We have found that the peptide was able to insert into membranes and permeabilize them while the native protein VP7 did not. Finally, NMR studies revealed that in a hydrophobic environment, this helix has amphipathic properties characteristic of membrane-perforating peptides. Surprisingly, its structure varies from that of its counterpart in the structure of the native protein VP7, as was determined by X-ray. All together, our results show that a peptide released from VP7 is capable of changing its conformation and destabilizing artificial membranes. Such peptides could play an important role by facilitating membrane crossing by non-enveloped viruses during cell infection.
Keywords: ATR-FTIR; Circular dichroism; Conformational rearrangement; Membranotropic peptide; NMR; Plasmon waveguide resonance.
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