title: 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.
abstract: 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.
authors.affiliation: Department of Mammalian Virology, Institute for Animal Science and Health (ID-DLO), Lelystad, The Netherlands. J.P.M.Langedijk@id.dlo.nl
authors.forename: J P
authors.initials: JP
authors.lastname: Langedijk
authors.forename: B L
authors.initials: BL
authors.lastname: de Groot
authors.forename: H J
authors.initials: HJ
authors.lastname: Berendsen
authors.forename: J T
authors.initials: JT
authors.lastname: van Oirschot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry*; D003198:Computer Simulation; D017124:Conserved Sequence; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012136:Respiratory Syncytial Viruses / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D015703:Antigens, CD; C066028:G protein, Bovine respiratory syncytial virus; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014759:Viral Envelope Proteins