Paramyxoviruses are responsible for significant human mortality and disease worldwide, but the molecular mechanisms underlying their entry into host cells remain poorly understood. We have solved the crystal structure of a fragment of the simian parainfluenza virus 5 fusion protein (SV5 F), revealing a 96 Å long coiled coil surrounded by three antiparallel helices. This structure places the fusion and transmembrane anchor of SV5 F in close proximity with a large intervening domain at the opposite end of the coiled coil. Six amino acids, potentially part of the fusion peptide, form a segment of the central coiled coil, suggesting that this structure extends into the membrane. Deletion mutants of SV5 F indicate that putative flexible tethers between the coiled coil and the viral membrane are dispensable for fusion. The lack of flexible tethers may couple a final conformational change in the F protein directly to the fusion of two bilayers.
|Number of pages||11|
|State||Published - Mar 1999|
Bibliographical noteFunding Information:
We thank Helen Mercer for excellent technical assistance and Beth Wurzburg and Scott Garman for help in synchrotron data collection and for useful discussions. To our regret, space requirements limit the referencing of many other relevant studies. Portions of this work were performed at the DND-CAT Synchrotron Research Center of the Advanced Photon Source and at the Stanford Synchrotron Radiation Laboratory (SSRL), operated by the Department of Energy. This research was supported by Public Health Service research grants AI-38972 (T. S. J.) and AI-23173 (R. A. L.) from the National Institute of Allergy and Infectious Diseases. R. E. D. is supported by Public Health Service NRSA F32 AI-09607. R. E. D. was an Associate and R. A. L. is an Investigator of the Howard Hughes Medical Institute. T. S. J. is a Pew Scholar in the Biomedical Sciences.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology