Modulation of the activities of HN protein of Newcastle disease virus by nonconserved cysteine residues.
Comparisons of the sequences of the hemagglutinin-neuraminidase (HN) protein from thirteen different strains of Newcastle disease virus (NDV) show that while 12 cysteine residues are conserved in all strains, two cysteine residues are variably present (Sakaguchi et al. (1989) Virology 169, 260-272). One of these residues, at amino acid 6, is in the cytoplasmic domain. The other cysteine is at amino acid 123 in the ectodomain and is responsible for disulfide-linked HN dimers detected in some NDV strains (McGinnes and Morrison (1994) Virology 200, 470-483). To explore the role of these nonconserved residues in the structure and function of the protein, cysteine residues at amino acid 6 and 123 in the HN protein of the AV strain of NDV were mutated individually and in combination by site specific mutagenesis to serine and tryptophan, respectively. Proteins with mutations in either residue (C6S or C123W) or in both residues (C6S,123W) were transported to the cell surface. However, all three mutants had reduced attachment, neuraminidase, and fusion promotion activities. All three mutant proteins also showed an alteration in an antigenic site specific for oligomers of HN protein while all other antigenic sites were present at wild type levels. These results suggest that the nonconserved cysteine residues in the HN sequence may modulate the biological activities of the protein by affecting the oligomeric structure of the protein.
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
L W
LW
McGinnes
T G
TG
Morrison
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D003545:Cysteine / Q000502:physiology*; D015707:HN Protein / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009522:Newcastle disease virus / Q000502:physiology*; D011487:Protein Conformation; D014162:Transfection
D000914:Antibodies, Viral; D015707:HN Protein; D003545:Cysteine