The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral membrane-fusion proteins. How these diminutive fusogens mediate cell–cell fusion and syncytium formation is unclear. Ongoing efforts are aimed at defining the roles of the FAST protein ecto-, endo- and transmembrane domains in the membrane-fusion reaction. We now provide direct evidence for homomultimer formation by the FAST proteins by using an anti-haemagglutinin (HA) mAb to co-precipitate the untagged p14 FAST protein from cells co-transfected with HA-tagged p14. Disrupting the intracellular endoplasmic reticulum–Golgi complex vesicle transport pathway prevented p14 homomultimer formation, while lower pH disrupted p14 multimers. The p14 endodomain or transmembrane domains are not required for multimer formation, which, along with the pH sensitivity and the distribution of histidine residues, suggests the 36 aa p14 ectodomain is a multimerization motif.


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  1. Arvan, P., Zhang, B. Y., Feng, L., Liu, M. & Kuliawat, R.(2002). Lumenal protein multimerization in the distal secretory pathway/secretory granules. Curr Opin Cell Biol 14, 448–453.[CrossRef] [Google Scholar]
  2. Brown, C. W., Stephenson, K. B., Hanson, S., Kucharczyk, M., Duncan, R., Bell, J. C. & Lichty, B. D.(2009). The p14 FAST protein of reptilian reovirus increases vesicular stomatitis virus neuropathogenesis. J Virol 83, 552–561.[CrossRef] [Google Scholar]
  3. Cheng, L. T., Plemper, R. K. & Compans, R. W.(2005). Atypical fusion peptide of Nelson Bay virus fusion-associated small transmembrane protein. J Virol 79, 1853–1860.[CrossRef] [Google Scholar]
  4. Clancy, E. K. & Duncan, R.(2009). Reovirus FAST protein transmembrane domains function in a modular, primary sequence-independent manner to mediate cell–cell membrane fusion. J Virol 83, 2941–2950.[CrossRef] [Google Scholar]
  5. Corcoran, J. A. & Duncan, R.(2004). Reptilian reovirus utilizes a small type III protein with an external myristylated amino terminus to mediate cell–cell fusion. J Virol 78, 4342–4351.[CrossRef] [Google Scholar]
  6. Corcoran, J. A., Syvitski, R., Top, D., Epand, R. M., Epand, R. F., Jakeman, D. & Duncan, R.(2004). Myristoylation, a protruding loop, and structural plasticity are essential features of a nonenveloped virus fusion peptide motif. J Biol Chem 279, 51386–51394.[CrossRef] [Google Scholar]
  7. Corcoran, J. A., Salsman, J., de Antueno, R., Touhami, A., Jericho, M. H., Clancy, E. K. & Duncan, R.(2006). The p14 fusion-associated small transmembrane (FAST) protein effects membrane fusion from a subset of membrane microdomains. J Biol Chem 281, 31778–31789.[CrossRef] [Google Scholar]
  8. Dawe, S. & Duncan, R.(2002). The S4 genome segment of baboon reovirus is bicistronic and encodes a novel fusion-associated small transmembrane protein. J Virol 76, 2131–2140.[CrossRef] [Google Scholar]
  9. Dawe, S., Corcoran, J. A., Clancy, E. K., Salsman, J. & Duncan, R.(2005). Unusual topological arrangement of structural motifs in the baboon reovirus fusion-associated small transmembrane protein. J Virol 79, 6216–6226.[CrossRef] [Google Scholar]
  10. Donaldson, J. G., Lippincott-Schwartz, J., Bloom, G. S., Kreis, T. E. & Klausner, R. D.(1990). Dissociation of a 110-kD peripheral membrane protein from the Golgi apparatus is an early event in brefeldin A action. J Cell Biol 111, 2295–2306.[CrossRef] [Google Scholar]
  11. Klausner, R. D., Donaldson, J. G. & Lippincott-Schwartz, J.(1992). Brefeldin A: insights into the control of membrane traffic and organelle structure. J Cell Biol 116, 1071–1080.[CrossRef] [Google Scholar]
  12. Melikyan, G. B.(2008). Common principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm. Retrovirology 5, 111.[CrossRef] [Google Scholar]
  13. Racine, T., Hurst, T., Barry, C., Shou, J., Kibenge, F. & Duncan, R.(2009). Aquareovirus effects syncytiogenesis by using a novel member of the FAST protein family translated from a noncanonical translation start site. J Virol 83, 5951–5955.[CrossRef] [Google Scholar]
  14. Salsman, J., Top, D., Boutilier, J. & Duncan, R.(2005). Extensive syncytium formation mediated by the reovirus FAST proteins triggers apoptosis-induced membrane instability. J Virol 79, 8090–8100.[CrossRef] [Google Scholar]
  15. Shmulevitz, M. & Duncan, R.(2000). A new class of fusion-associated small transmembrane (FAST) proteins encoded by the non-enveloped fusogenic reoviruses. EMBO J 19, 902–912.[CrossRef] [Google Scholar]
  16. Shmulevitz, M., Salsman, J. & Duncan, R.(2003). Palmitoylation, membrane-proximal basic residues, and transmembrane glycine residues in the reovirus p10 protein are essential for syncytium formation. J Virol 77, 9769–9779.[CrossRef] [Google Scholar]
  17. White, J. M., Delos, S. E., Brecher, M. & Schornberg, K.(2008). Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Crit Rev Biochem Mol Biol 43, 189–219.[CrossRef] [Google Scholar]

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