Molecular modelling and epitope prediction of gp29 from lymphatic filariae.
The sequence of the major soluble protein component of the cuticle of filarial nematodes is homologous to that of bovine glutathione peroxidase, for which an X-ray structure is available. Due to the high degree of sequence identity (42%), it has been possible to build an apparently reliable three-dimensional model of the gp29 cuticular protein from Brugia spp. that will aid studies of the molecule both as a target immunogen and secreted enzyme. The modelled core of the gp29 structure is conserved compared to the bovine enzyme, consisting of a beta-sheet surrounded by alpha-helices. Experimental data showed that Brugia spp. gp29 has four subunits, and a tetrameric form of gp29 has also been modelled. The two N-linked glycosylation sites per subunit were predicted to lie on the surface of the tetramer. Most of the variation in amino acid sequence compared to that of mammalian enzymes, occurs in the surface loops, several of which are larger and more exposed in gp29. Deglycosylated gp29 was demonstrated to be immunogenic in human infection, and six likely B-cell epitopes have been predicted on the basis of a high protrusion index and sequence variability.
Zvelebil
M J
MJ
Wellcome Centre for Parasitic Infections, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
Tang
L
L
Cookson
E
E
Selkirk
M E
ME
Thornton
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001665:Binding Sites; D017178:Brugia malayi / Q000201:enzymology / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005979:Glutathione Peroxidase / Q000276:immunology*; D006031:Glycosylation; D015801:Helminth Proteins / Q000276:immunology*; D008208:Lymphatic System / Q000469:parasitology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment
D000947:Antigens, Helminth; D000939:Epitopes; D015801:Helminth Proteins; D005979:Glutathione Peroxidase; C080439:selenium-independent glutathione peroxidase