title: Amino acid substitutions in the F-specific domain in the stalk of the newcastle disease virus HN protein modulate fusion and interfere with its interaction with the F protein.
abstract: The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus mediates attachment to sialic acid receptors, as well as cleavage of the same moiety. HN also interacts with the other viral glycoprotein, the fusion (F) protein, to promote membrane fusion. The ectodomain of the HN spike consists of a stalk and a terminal globular head. The most conserved part of the stalk consists of two heptad repeats separated by a nonhelical intervening region (residues 89 to 95). Several amino acid substitutions for a completely conserved proline residue in this region not only impair fusion and the HN-F interaction but also decrease neuraminidase activity in the globular domain, suggesting that the substitutions may alter HN structure. Substitutions for L94 also interfere with fusion and the HN-F interaction but have no significant effect on any other HN function. Amino acid substitutions at other positions in the intervening region also modulate only fusion. In all cases, diminished fusion correlates with a decreased ability of the mutated HN protein to interact with F at the cell surface. These findings indicate that the intervening region is critical to the role of HN in the promotion of fusion and may be directly involved in its interaction with the homologous F protein.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655-0122, USA.
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Melanson
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Iorio
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D006224:Cricetinae; D015707:HN Protein / Q000737:chemistry* / Q000502:physiology; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000378:metabolism; D009522:Newcastle disease virus / Q000737:chemistry / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D014760:Viral Fusion Proteins / Q000502:physiology*
chemical_list: D015707:HN Protein; D011991:Receptors, Virus; D014760:Viral Fusion Proteins; D009439:Neuraminidase