Journal article
Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling
Journal of virology, Vol.81(9), pp.4520-4532
05/2007
Handle:
https://hdl.handle.net/2376/108394
PMCID: PMC1900187
PMID: 17301148
Abstract
The cytoplasmic tails of the envelope proteins from multiple viruses are known to contain determinants that affect their fusogenic capacities. Here we report that specific residues in the cytoplasmic tail of the Nipah virus fusion protein (NiV-F) modulate its fusogenic activity. Truncation of the cytoplasmic tail of NiV-F greatly inhibited cell-cell fusion. Deletion and alanine scan analysis identified a tribasic KKR motif in the membrane-adjacent region as important for modulating cell-cell fusion. The K1A mutation increased fusion 5.5-fold, while the K2A and R3A mutations decreased fusion 3- to 5-fold. These results were corroborated in a reverse-pseudotyped viral entry assay, where receptor-pseudotyped reporter virus was used to infect cells expressing wild-type or mutant NiV envelope glycoproteins. Differential monoclonal antibody binding data indicated that hyper- or hypofusogenic mutations in the KKR motif affected the ectodomain conformation of NiV-F, which in turn resulted in faster or slower six-helix bundle formation, respectively. However, we also present evidence that the hypofusogenic phenotypes of the K2A and R3A mutants were effected via distinct mechanisms. Interestingly, the K2A mutant was also markedly excluded from lipid rafts, where ∼20% of wild-type F and the other mutants can be found. Finally, we found a strong negative correlation between the relative fusogenic capacities of these cytoplasmic-tail mutants and the avidities of NiV-F and NiV-G interactions (
P
= 0.007,
r
2
= 0.82). In toto, our data suggest that inside-out signaling by specific residues in the cytoplasmic tail of NiV-F can modulate its fusogenicity by multiple distinct mechanisms.
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Details
- Title
- Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling
- Creators
- Hector C Aguilar - Department of Microbiology, Immunology, and Molecular GeneticsKenneth A Matreyek - Department of Microbiology, Immunology, and Molecular GeneticsDaniel Y Choi - Department of Microbiology, Immunology, and Molecular GeneticsClaire Marie Filone - Department of Microbiology, Immunology, and Molecular GeneticsSophia Young - Department of Microbiology, Immunology, and Molecular GeneticsBenhur Lee - Department of Microbiology, Immunology, and Molecular Genetics
- Publication Details
- Journal of virology, Vol.81(9), pp.4520-4532
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- American Society for Microbiology
- Identifiers
- 99900548578201842
- Language
- English
- Resource Type
- Journal article