Structural Homology of the Central Conserved Region of the Attachment Protein G of Respiratory Syncytial Virus with the Fourth Subdomain of 55-kDa Tumor Necrosis Factor Receptor

• Published in: Virology (New York, N.Y.) Vol. 243; no. 2; pp. 293 - 302
• Main Authors: Langedijk, Johannes P.M., de Groot, Bert L., Berendsen, Herman J.C., van Oirschot, Jan T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.04.1998
• Subjects: Amino Acid Sequence; Animals; Antigens, CD - chemistry; Computer Simulation; Conserved Sequence; cystine noose; homology modeling; Humans; ID Lelystad, Institute for Animal Science and Health; ID-Lelystad, Instituut voor Dierhouderij en Diergezondheid; Mice; Models, Molecular; Molecular Dynamics; Molecular Sequence Data; Protein Conformation; Rats; Receptors, Tumor Necrosis Factor - chemistry; Receptors, Tumor Necrosis Factor, Type I; Respiratory Syncytial Viruses - chemistry; RSV; Sequence Homology, Amino Acid; Swine; TNFr; Viral Envelope Proteins - chemistry; TNFr; Molecular Dynamics; cystine noose; homology modeling; RSV
• DOI: 10.1006/viro.1998.9066
• ISSN: 0042-6822

The attachment protein G of respiratory syncytial virus (RSV) has a modular architecture. The ectodomain of the protein comprises a small folded conserved region which is bounded by two mucin-like regions. In this study, a sequence and structural homology is described between this central conserved region of RSV-G and the fourth subdomain of the 55-kDa tumor necrosis factor receptor (TNFr). The three-dimensional structures of RSV-G and human TNFr were previously determined with NMR spectroscopy and X-ray crystallography, respectively. The C-terminal part of both subdomains fold into a cystine noose connected by two cystine bridges with the same spacing between cysteine residues and the same topology. Although a general structural similarity is observed, there are differences in secondary structure and other structural features. Molecular Dynamics calculations show that the BRSV-G NMR structure of the cystine noose is stable and that the TNFr crystal structure of the cystine noose drifts towards the BRSV-G NMR structure in the simulated solution environment. By homology modelling a model was built for the unresolved N-terminal part of the central conserved region of RSV-G. The functions for both protein domains are not known but the structural similarity of both protein domains suggests a similar function. Although the homology suggests that the cystine noose of RSV-G may interfere with the antiviral and apoptotic effect of TNF, the biological activity remains to be proven.