Paramyxovirus fusion (F) protein: A conformational change on cleavage activation

Rebecca Ellis Dutch, Ryan N. Hagglund, Margaret A. Nagel, Reay G. Paterson, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The fusion (F) protein of the paramyxovirus SV5 promotes both virus-cell and cell-cell fusion. Recently, the atomic structure at 1.4 Å of an extremely thermostable six-helix bundle core complex consisting of two heptad repeat regions of the F protein has been described (K. A. Baker, R. E. Dutch, R. A. Lamb, and T. S. Jardetsky, Mol. Cell 3, 309-319, 1999). To analyze the conformations of the F protein at various stages of the membrane fusion process and to understand further the role of formation of the six-helix bundle core complex in promotion of membrane fusion, antibodies to peptides corresponding to regions of the F protein were obtained. Major changes in F protein antibody recognition were found after cleavage of the precursor protein F0 to the fusogenically active disulfide-linked heterodimer, F1 + F2, and antibodies directed against the heptad repeat regions recognized only the uncleaved form. A monoclonal antibody directed against the F protein showed increased recognition at the cell surface of the cleaved form of the F protein as compared to uncleaved F protein, again indicating changes in conformation between the uncleaved and cleaved forms of the F protein. Anti-peptide antibodies specific for the heptad repeat regions were unable to precipitate a synthetic protein that consisted of the heptad repeat regions separated only by a small spacer, suggesting that the antibodies are unable to recognize their target regions when the heptad repeats are present in the six-helix bundle core complex. Taken together, these data indicate that the six-helix bundle core complex is not present in the precursor molecule F0 and that significant conformational changes occur subsequent to cleavage of the F protein.

Original languageEnglish (US)
Pages (from-to)138-150
Number of pages13
JournalVirology
Volume281
Issue number1
DOIs
StatePublished - Mar 1 2001

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Paramyxovirus fusion (F) protein: A conformational change on cleavage activation'. Together they form a unique fingerprint.

Cite this