Amino acid substitutions in a conserved region in the stalk of the Newcastle disease virus HN glycoprotein spike impair its neuraminidase activity in the globular domain.
The ectodomain of the paramyxovirus haemagglutinin-neuraminidase (HN) glycoprotein spike can be divided into two regions: a membrane-proximal, stalk-like structure and a terminal globular domain. The latter contains all the antibody recognition sites of the protein, as well as its receptor recognition and neuraminidase (NA) active sites. These two activities of the protein can be separated by monoclonal antibody functional inhibition studies and mutations in the globular domain. Herein, we show that mutation of several conserved residues in the stalk of the Newcastle disease virus HN protein markedly decrease its NA activity without a significant effect on receptor recognition. Thus, mutations in the stalk, distant from the NA active site in the globular domain, can also separate attachment and NA. These results add to an increasing body of evidence that the NA activity of this protein is dependent on an intact stalk structure.
Wang
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Iorio
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D000327:Adsorption; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D017124:Conserved Sequence; D000939:Epitopes; D004912:Erythrocytes / Q000378:metabolism; D006168:Guinea Pigs; D015707:HN Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000378:metabolism; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009522:Newcastle disease virus / Q000201:enzymology* / Q000235:genetics; D011487:Protein Conformation; D012794:Sialic Acids / Q000378:metabolism; D014162:Transfection
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015707:HN Protein; D012794:Sialic Acids; C000020:N-acetylneuraminoyllactose; D009439:Neuraminidase; D007785:Lactose