Deduced structural model for animal rhabdovirus glycoproteins

The G protein sequences of fourteen animal rhabdoviruses, representing all four recognized genera (Vesiculovirus, Lyssavirus, Ephemerovirus and Novirhabdovirus) and the ungrouped sigma virus, were aligned using CLUSTAL W and adjusted to account for obvious sequence similarities not detected by the algorithm. Analysis of the alignment indicated remarkable preservation of G protein structural features including cysteine residues, antigenic sites and significant elements of secondary structure (alpha-helices, beta-strands and loops). Twelve highly conserved cysteine residues were assigned numbers (C-I to C-XII) according to their location in the alignment. Other cysteine residues were assigned numbers (C-O to C-XIIe) according to their position relative to the conserved cysteines, The pattern of conservation of cysteine residues and the structural characteristics of identified discontinuous antigenic sites were used to deduce a model for G protein structure. Six absolutely conserved cysteines are predicted to associate in three disulphide bridges (C-I-C-XII; C-VIII-C-XI; C-IX-C-X) that form the core of the G protein structure and define the common discontinuous antigenic site. The associations of six other highly conserved cysteines (C-II-C-IV; C-III-C-V; C-VI-C-VII) are predicted by the absence of a specific pair in all viruses within a genus. Of the other cysteines, one pair occurs only in ephemeroviruses and novirhabdoviruses (C-O-C-XIIa); two pairs occur only in ephemeroviruses (C-Ib-C-VIIIa; C-XIIb-C-XIIe); and two pairs occur only in lyssaviruses (C-Ia-C-VIIIb; C-XIIc-C-XIId). The structures predicted by the model account for the preservation of conformational antigenic sites, accommodate genus-specific variations, and are generally consistent with previous observations of G protein structure.