Role of a conserved sequence in the maturation and function of the NDV HN glycoprotein.
The hemagglutinin-neuraminidase (HN) proteins of viruses in the Paramyxovirus genus have a short conserved sequence, G(A, S)EGR(I, L, V). The role of this sequence in the intracellular processing and function of the Newcastle disease virus HN protein was explored by site directed mutagenesis. Mutations in this region fall into two categories. One set of mutants (G398A, E400D, R402K, and a deletion removing amino acids 400-403) was defective in folding. These mutant proteins formed little or no mature, disulfide linked oligomer. They had few or no antigenic sites found on the mature protein and they were transported to the cell surface poorly or not at all. The second class of mutants (A399G, G401A, G401L) was minimally affected in folding and intracellular transport. When normalized to surface expression, this group of mutant proteins had wild type levels of attachment activity, neuraminidase activity, and fusion promotion activity. Thus mutations in this region directly affect intracellular processing but not the biological activities of the protein. This sequence may, therefore, be conserved in the HN proteins of Paramyxoviruses because it is critical to the folding of the molecule.
Sergel
T
T
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
McGinnes
L
L
Morrison
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D004279:DNA, Viral / Q000235:genetics; D015707:HN Protein / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009522:Newcastle disease virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D011499:Protein Processing, Post-Translational
D000956:Antigens, Viral; D004279:DNA, Viral; D015707:HN Protein