Solution Structure of the Immunodominant Region of Protein G of Bovine Respiratory Syncytial Virus^,

Abstract

The three-dimensional solution structure of the immunodominant central conserved region of the attachment protein G (BRSV-G) of bovine respiratory syncytial virus has been determined by nuclear magnetic resonance (NMR) spectroscopy. In the 32-residue peptide studied, 19 residues form a small rigid core composed of two short helices, connected by a type I' turn, and linked by two disulfide bridges. This unique fold is among the smallest stable tertiary structures known and could therefore serve as an ideal building block for the design of de novo proteins and as a test case for modeling studies. A characteristic hydrophobic pocket, lined by conserved residues, lies at the surface of the peptide and may play a role in receptor binding. This work provides a structural basis for further peptide vaccine development against the severe diseases associated with the respiratory syncytial viruses in both cattle and man.

Antigenic structure of the human respiratory syncytial virus G glycoprotein and relevance of hypermutation events for the generation of antigenic variants.

“…This may reflect severe structural and \or functional restrictions at these sites. In fact, residues 171 and 172 are found at the bottom and residue 173 at the left of the putative receptor binding pocket proposed by Doreleijers et al (1996). In contrast, some of the amino acid changes selected in the hypermutated viruses are also found in bovine and ovine G protein sequences.…”

“…3). Amino acid 181 is included in the cysteine noose motif proposed by Doreleijers et al (1996) for the three-dimensional structure of a central segment of the G protein ectodomain whereas amino acid 188 is outside that motif. Moreover, the reactivity of antibodies 021\18G and 021\19G with the escape mutants of Fig.…”

Monoclonal antibody neutralization escape mutants of respiratory syncytial virus with unique alterations in the attachment (G) protein.

“…The longest stretch of exact identity in the ectodomain is a 13 amino acid region in the mid-portion of the molecule which is completely conserved among all naturally occurring RSV strains of either group analysed thus far (Cane et al, 1991 ;Garcia et al, 1994 ;Sullender et al, 1991). This region, which encompasses amino acids 164-176, includes the first two of the four conserved cysteine residues proposed to form a cysteine noose which contributes to the structural integrity of G Doreleijers et al, 1996). Because this region is so highly conserved among RSV isolates it is speculated that it either possesses cell receptor-binding activity or provides critically important structural support for this activity.…”

The antigenic and genetic variability of bovine respiratory syncytial virus with emphasis on the G protein

“…Based on the similarity of the "hydropathy profile" in bovine and human RSV we can assume that the general structure of both the proteins is identical (Doreleijers et al, 1996;Lerch et al, 1990). Glycoprotein G is composed of three parts (domains): cytoplasmatic (AA 1-37), transmembrane (AA 38-65) and extracellular (AA 66-257) (ectodomain) .…”

“…The extracellular part of glycoprotein G is responsible for binding the virus to the sensitive cells, and the greatest differences within all viral proteins are localized there (Lerch et al, 1990). The ectodomain of the virus consists of a hydrophobic, conserved central area, flanked by hydrophilic variable regions (Doreleijers et al, 1996;Langedijk et al, 1996). The variable regions of the protein are called mucin-like due to their high content of carbohydrate side-chains bounded to Ser, Thr (O-linked sugars), and Pro (N-linked sugars).…”