Structure of the uncleaved ectodomain of the paramyxovirus (hPIV3) fusion protein.
Class I viral fusion proteins share common mechanistic and structural features but little sequence similarity. Structural insights into the protein conformational changes associated with membrane fusion are based largely on studies of the influenza virus hemagglutinin in pre- and postfusion conformations. Here, we present the crystal structure of the secreted, uncleaved ectodomain of the paramyxovirus, human parainfluenza virus 3 fusion (F) protein, a member of the class I viral fusion protein group. The secreted human parainfluenza virus 3 F forms a trimer with distinct head, neck, and stalk regions. Unexpectedly, the structure reveals a six-helix bundle associated with the postfusion form of F, suggesting that the anchor-minus ectodomain adopts a conformation largely similar to the postfusion state. The transmembrane anchor domains of F may therefore profoundly influence the folding energetics that establish and maintain a metastable, prefusion state.
Yin
Hsien-Sheng
HS
Department of Biochemistry, Molecular Biology, and Cell Biology, Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208-3500, USA.
Paterson
Reay G
RG
Wen
Xiaolin
X
Lamb
Robert A
RA
Jardetzky
Theodore S
TS
D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D007313:Insecta; D008561:Membrane Fusion; D008958:Models, Molecular; D009154:Mutation; D018098:Paramyxovirinae / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry*
D018076:DNA, Complementary; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins