title: A peptide derived from the rotavirus outer capsid protein VP7 permeabilizes artificial membranes.
abstract: 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.
authors.affiliation: LCRB, CNRS (UMR 8015), Université Paris Descartes, F-75270 Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Elaid
authors.affiliation: LVMS, CNRS (UPR 3296), F-91198 Gif-sur-Yvette, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Libersou
authors.affiliation: LVMS, CNRS (UPR 3296), F-91198 Gif-sur-Yvette, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Ouldali
authors.affiliation: LCRB, CNRS (UMR 8015), Université Paris Descartes, F-75270 Paris, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Morellet
authors.affiliation: CBMN, CNRS (UMR 5248), Université Bordeaux, 33600 Pessac, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Desbat
authors.affiliation: CBMN, CNRS (UMR 5248), Université Bordeaux, 33600 Pessac, France.
authors.forename: Isabel D
authors.initials: ID
authors.lastname: Alves
authors.affiliation: LVMS, CNRS (UPR 3296), F-91198 Gif-sur-Yvette, France. Electronic address: Jean.Lepault@vms.cnrs-gif.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Lepault
authors.affiliation: LCRB, CNRS (UMR 8015), Université Paris Descartes, F-75270 Paris, France. Electronic address: serge.bouaziz@parisdescartes.fr.
authors.forename: Serge
authors.initials: S
authors.lastname: Bouaziz
mesh_terms: D000956:Antigens, Viral / Q000737:chemistry / Q000378:metabolism*; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D019295:Computational Biology; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D008567:Membranes, Artificial; D008823:Micelles; D010446:Peptide Fragments; C050779:VP7 protein, Rotavirus
keywords: ATR-FTIR; Circular dichroism; Conformational rearrangement; Membranotropic peptide; NMR; Plasmon waveguide resonance