Sequence and structure alignment of Paramyxoviridae attachment proteins and discovery of enzymatic activity for a morbillivirus hemagglutinin

J Virol. 1997 Aug;71(8):6155-67. doi: 10.1128/JVI.71.8.6155-6167.1997.

Abstract

On the basis of the conservation of neuraminidase (N) active-site residues in influenza virus N and paramyxovirus hemagglutinin-neuraminidase (HN), it has been suggested that the three-dimensional (3D) structures of the globular heads of the two proteins are broadly similar. In this study, details of this structural similarity are worked out. Detailed multiple sequence alignment of paramyxovirus HN proteins and influenza virus N proteins was based on the schematic representation of the previously proposed structural similarity. This multiple sequence alignment of paramyxovirus HN proteins was used as an intermediate to align the morbillivirus hemagglutinin (H) proteins with neuraminidase. Hypothetical 3D structures were built for paramyxovirus HN and morbillivirus H, based on homology modelling. The locations of insertions and deletions, glycosylation sites, active-site residues, and disulfide bridges agree with the proposed 3D structure of HN and H of the Paramyxoviridae. Moreover, details of the modelled H protein predict previously undescribed enzymatic activity. This prediction was confirmed for rinderpest virus and peste des petits ruminants virus. The enzymatic activity was highly substrate specific, because sialic acid was released only from crude mucins isolated from bovine submaxillary glands. The enzymatic activity may indicate a general infection mechanism for respiratory viruses, and the active site may prove to be a new target for antiviral compounds.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Chlorocebus aethiops
  • Disulfides / chemistry
  • Epitopes
  • Glycosylation
  • HN Protein / chemistry*
  • Hemagglutinins, Viral / chemistry*
  • Molecular Sequence Data
  • Morbillivirus / chemistry*
  • Neuraminidase / chemistry
  • Paramyxoviridae / chemistry*
  • Sequence Alignment
  • Substrate Specificity
  • Vero Cells

Substances

  • Disulfides
  • Epitopes
  • HN Protein
  • Hemagglutinins, Viral
  • Neuraminidase

Associated data

  • GENBANK/A00885
  • GENBANK/A24004
  • GENBANK/A27005
  • GENBANK/A27006
  • GENBANK/A33777
  • GENBANK/B27218
  • GENBANK/B38480
  • GENBANK/B38520
  • SWISSPROT/P29767
  • SWISSPROT/P29768
  • SWISSPROT/S20590
  • SWISSPROT/S32016