title: Participation of two fusion peptides in measles virus-induced membrane fusion: emerging similarity with other paramyxoviruses.
abstract: Paramyxoviruses penetrate into their host cells by fusing their membranes with the plasma membrane. The hydrophobic N terminus of their F1 protein, termed the 'fusion peptide', is thought to be responsible for this process. Recently, an additional internal fusion peptide, homologous in sequence to the N-terminal fusion peptide of HIV-1, was identified in the Sendai virus F1 protein. Here, we investigated whether the presence of an additional internal fusion peptide is a general feature of paramyxoviridae. To this end, we synthesized and structurally and functionally characterized three peptides: (i) MV-197, which corresponds to an internal segment of the F1 protein of the measles virus (amino acids 197-225), homologous in location but not in sequence to the internal fusion peptide of the Sendai virus, (ii) Mu-MV-197, a randomized version of MV-197, and (iii) the 33 amino acid N-terminal fusion peptide of the measles virus. Remarkably, only MV-197 was highly fusogenic toward large unilamellar vesicles composed of either zwitterionic (phosphatidylcholine or phosphatidylcholine/sphingomyelin/cholesterol, a composition similar to that of human cell membranes) or negatively charged phospholipids. Binding experiments, circular dichroism spectroscopy in phospholipid membranes, and homo energy-transfer studies with fluorescently labeled peptides revealed that MV-197 adopts a predominant alpha-helical structure and shares properties similar to those reported for known fusion peptides. These results suggest that the presence of two fusion peptides in the F1 protein is a general feature of paramyxoviruses.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Samuel
authors.forename: Y
authors.initials: Y
authors.lastname: Shai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019286:Endopeptidase K / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008459:Measles virus / Q000378:metabolism / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D018108:Respirovirus / Q000502:physiology*; D012996:Solutions; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D016662:Virus Integration
chemical_list: D008051:Lipid Bilayers; D010446:Peptide Fragments; D010455:Peptides; D012996:Solutions; D014760:Viral Fusion Proteins; D019286:Endopeptidase K