Structural and functional relationship between the receptor recognition and neuraminidase activities of the Newcastle disease virus hemagglutinin-neuraminidase protein: receptor recognition is dependent on neuraminidase activity.
The terminal globular domain of the paramyxovirus hemagglutinin-neuraminidase (HN) glycoprotein spike has a number of conserved residues that are predicted to form its neuraminidase (NA) active site, by analogy to the influenza virus neuraminidase protein. We have performed a site-directed mutational analysis of the role of these residues in the functional activity of the Newcastle disease virus (NDV) HN protein. Substitutions for several of these residues result in a protein lacking both detectable NA and receptor recognition activity. Contribution of NA activity, either exogenously or by coexpression with another HN protein, partially rescues the receptor recognition activity of these proteins, indicating that the receptor recognition deficiencies of the mutated HN proteins result from their lack of detectable NA activity. In addition to providing support for the homology-based predictions for the structure of HN, these findings argue that (i) the HN residues that mediate its NA activity are not critical to its attachment function and (ii) NA activity is required for the protein to mediate binding to receptors.
Iorio
R M
RM
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0122, USA. Ronald.Iorio@umassmed.edu
Field
G M
GM
Sauvron
J M
JM
Mirza
A M
AM
Deng
R
R
Mahon
P J
PJ
Langedijk
J P
JP
D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D015707:HN Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009439:Neuraminidase / Q000378:metabolism*; D009522:Newcastle disease virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011991:Receptors, Virus / Q000378:metabolism*; D013329:Structure-Activity Relationship
D015707:HN Protein; D011991:Receptors, Virus; D009439:Neuraminidase