Structure−antigenicity relationship studies of the central conserved region of human respiratory syncytial virus protein G

• Published in: The journal of peptide research Vol. 60; no. 5; pp. 271 - 282
• Main Authors: Sugawara, M., Czaplicki, J., Ferrage, J., Milon, A., Haeuw, J.-F., Power, U. F., Corvaïa, N., Nguyen, T., Beck, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.11.2002; Wiley
• Subjects: Antigens, Viral - chemistry; Antigens, Viral - immunology; BBG2Na; Biochemical Research Methods; Biochemistry & Molecular Biology; Circular Dichroism; exchange rate of NH protons; Humans; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; NMR; peptide structure and dynamics; Protein Conformation; Respiratory Syncytial Virus Vaccines - chemistry; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - chemistry; Respiratory Syncytial Virus, Human - immunology; RSV vaccine; Science & Technology; Structure-Activity Relationship; Vaccines, Subunit - chemistry; Vaccines, Subunit - immunology; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - immunology; ALBUMIN-BINDING REGION; RECOMBINANT SUBUNIT VACCINE; NUCLEAR-MAGNETIC-RESONANCE; CHEMICAL-SHIFT; G-GLYCOPROTEIN; circular dichroism; SUBGROUP-A; RSV vaccine; CIRCULAR-DICHROISM SPECTRA; NMR; IMMUNOGENICITY; exchange rate of NH protons; peptide structure and dynamics; SECONDARY STRUCTURE; BBG2Na
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1034/j.1399-3011.2002.21027.x

: BBG2Na is a recombinant protein, composed in part of carrier protein BB and of the central conserved domain of the attachment glycoprotein G of human respiratory syncytial virus (HRSV) subgroup A. This protein is a potent vaccine candidate against HRSV. G2Na contains several contiguous B‐cell epitopes, occupying sequential positions in the linear sequence of the protein. One of the epitopes contains four cysteines that are completely conserved in known strains of HRSV and form a ‘cysteine noose’ motif. In this study, we analysed circular dichroism (CD) spectra of BBG2Na and its B‐cell epitopes. We also used NMR and molecular dynamics simulations to determine the three‐dimensional structure of the cysteine noose domain. We observed significant structural differences related to the length of peptides containing the cysteine noose. These differences show good correlation with the immunogenic activity of the peptides. It is shown that a single Val171 addition induces a pronounced structure stabilization of the cysteine noose peptide G4a (1–4/2−3) (residues 172–187), which is associated with a 100‐fold increase in its antigenicity vis‐à‐vis a G‐protein specific monoclonal antibody.