Structural features of paramyxovirus F protein required for fusion initiation.
On the basis of the coordinates of the related Newcastle disease virus (NDV) F protein, Valine-94, a determinant of measles virus (MV) cytopathicity, is predicted to lie in a cylindrical cavity with 10 A diameter located at the F neck. A 16-residue domain around V94 is functionally interchangeable between NDV and MV F, supporting our homology model. Features of the cavity are conserved within the Paramyxovirinae. A hydrophobic base and a hydrophilic residue at the rim are required for surface expression. Small residue substitutions predicted to open the cavity were found to disrupt transport or limit fusogenicity of transport-competent mutants but can be compensated for by simultaneous insertion of larger residues at the opposing wall. Variants containing histidine substitutions mediate fusion at pH 8.5, while at pH 7.2 fusion is blocked, suggesting that functionality requires low charge in the cavity. These results indicate that specific structural features of the cavity are essential for paramyxovirus fusion initiation.
Plemper
Richard K
RK
Department of Microbiology and Immunology, School of Medicine, 3001 Rollins Research Center, 1510 Clifton Road, Emory University, Atlanta, Georgia 30322, USA.
Lakdawala
Ami S
AS
Gernert
Kim M
KM
Snyder
James P
JP
Compans
Richard W
RW
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008459:Measles virus / Q000737:chemistry / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D018108:Respirovirus / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014633:Valine / Q000737:chemistry / Q000235:genetics; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000502:physiology*
D008565:Membrane Proteins; D014760:Viral Fusion Proteins; D014633:Valine