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

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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
Pages (from-to)138-150
Number of pages13
Issue number1
StatePublished - Mar 1 2001

Bibliographical note

Funding Information:
This work was supported in part by Research Grant AI-23173 from the National Institute of Allergy and Infectious Disease. R.E.D. was supported in part by a Public Health Service NRSA F32 AI-09607. Part of this work was performed by R.N.H. toward an undergraduate Honors Thesis (1999) at Northwestern University. R.A.L. is an Investigator of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

  • Virology


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