Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation.
Enveloped viruses have evolved complex glycoprotein machinery that drives the fusion of viral and cellular membranes, permitting entry of the viral genome into the cell. For the paramyxoviruses, the fusion (F) protein catalyses this membrane merger and entry step, and it has been postulated that the F protein undergoes complex refolding during this process. Here we report the crystal structure of the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a carboxy-terminal trimerization domain. The structure of the F protein shows that there are profound conformational differences between the pre- and postfusion states, involving transformations in secondary and tertiary structure. The positions and structural transitions of key parts of the fusion machinery, including the hydrophobic fusion peptide and two helical heptad repeat regions, clarify the mechanism of membrane fusion mediated by the F protein.
Yin
Hsien-Sheng
HS
Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208-3500, USA.
Wen
Xiaolin
X
Paterson
Reay G
RG
Lamb
Robert A
RA
Jardetzky
Theodore S
TS
D018360:Crystallography, X-Ray; D008561:Membrane Fusion; D008958:Models, Molecular; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D018108:Respirovirus / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism
D014760:Viral Fusion Proteins; C072983:F protein, parainfluenza virus 3