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The synaptic SNARE complex is a parallel four-stranded helical bundle

Abstract

The heterotrimeric synaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of the synaptic vesicle-associated membrane protein 2 (VAMP2) and presynaptic plasma membrane proteins SNAP-25 (synaptosome-associated protein of 25,000 Mr) and syntaxin 1A, is a critical component of the exocytotic machinery. We have used spin labeling electron paramagnetic resonance spectroscopy to investigate the structural organization of this complex, particularly the two predicted helical domains contributed by SNAP-25. Our results indicate that the N- and C-terminal domains of SNAP-25 are parallel to each other and to the C-terminal domain of syntaxin 1A. Based on these findings, we propose a parallel four-stranded coiled coil model for the structure of the synaptic SNARE complex.

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Figure 1: Synaptic SNARE complexes assembled with wild type and spin-labeled proteins.
Figure 2: EPR spectra of synaptic SNARE complexes.
Figure 3: Schematic representation of SNARE complex components showing EPR-derived interspin distances.
Figure 4: The synaptic SNARE complex: a four-stranded helical bundle.

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References

  1. Bennett, M. K. & Scheller, R. Annu. Rev. Biochem 63, 63–100 (1994).

    Article  CAS  Google Scholar 

  2. Sudhof, T. C. Nature 375, 645–653 (1995).

    Article  CAS  Google Scholar 

  3. Niemann, H., Blasi, J. & Jahn, R. Trends Cell Biol. 4, 179–185 (1994).

    Article  CAS  Google Scholar 

  4. Hayashi, T. et al. EMBO J. 13, 5051–5061 (1994).

    Article  CAS  Google Scholar 

  5. Broadie, K. et al. Neuron 15, 663–673 (1995).

    Article  CAS  Google Scholar 

  6. Weber, T. et al. Cell 92, 759–772 (1998).

    Article  CAS  Google Scholar 

  7. Poirier, M. A. et al. J. Biol. Chem. 273, 11370–11377 (1998).

    Article  CAS  Google Scholar 

  8. Kee, Y., Lin, R. C., Hsu, S. C. & Scheller, R. H. Neuron 14, 991–998 (1995).

    Article  CAS  Google Scholar 

  9. Chapman, E. R., An, S., Barton, N. & Jahn, R. J. Biol. Chem. 269, 27427–27432 (1994).

    CAS  PubMed  Google Scholar 

  10. Lupas, A. Meth. Enz. 266, 513–525 (1996).

    Article  CAS  Google Scholar 

  11. Fasshauer, D., Bruns, D., Shen, B., Jahn, R. & Brunger, A. T. J. Biol. Chem. 272, 4582–4590 (1997).

    Article  CAS  Google Scholar 

  12. Fasshauer, D., Otto, H., Eliason, W. K., Jahn, R. & Brunger, A. T. J. Biol. Chem. 272, 28036–28041 (1997).

    Article  CAS  Google Scholar 

  13. Hanson, P. I., Roth, R., Morisaki, H., Jahn, R. & Heuser, J. E. Cell 90, 523–535 (1997).

    Article  CAS  Google Scholar 

  14. Lin, R. C. & Scheller, R. H. Neuron 19, 1087–1094 (1997).

    Article  CAS  Google Scholar 

  15. Otto, H., Hanson, P. I. & Jahn, R. Proc. Natl. Acad. Sci. USA 94, 6197–6201 (1997).

    Article  CAS  Google Scholar 

  16. Hao, J. C., Salem, N., Peng, X. R., Kelly, R. B. & Bennett, M. K. J. Neurosci. 17, 1596–1603 (1997).

    Article  CAS  Google Scholar 

  17. Mchaourab, H. S., Lietzow, M. A., Hideg, K. & Hubbell, W. L. Biochemistry 35, 7692–7704 (1996).

    Article  CAS  Google Scholar 

  18. Rabenstein, M. D. & Shin, Y.-K. Biochemistry 35, 13922–13928 (1996).

    Article  CAS  Google Scholar 

  19. Kim, C.-H., Macosko, J. C. & Shin, Y.-K. Biochemistry 37, 137–144 (1998).

    Article  CAS  Google Scholar 

  20. Weimbs, T., et al. Proc. Natl. Acad. Sci. USA 94, 3046–3051 (1997).

    Article  CAS  Google Scholar 

  21. Kim, C.-H., Macosko, J. C., Yu, Y. G. & Shin, Y.-K. Biochemistry 35, 5359–5365 (1996).

    Article  CAS  Google Scholar 

  22. Rabenstein, M. D. & Shin, Y.-K. Proc. Natl. Acad. Sci. USA 92, 8239–8243 (1995).

    Article  CAS  Google Scholar 

  23. Weimbs, T., Mostov, K. E., Low, S. H. & Hofman, K. Trends Cell Biol. 8, 260–262 (1998).

    Article  CAS  Google Scholar 

  24. Shin, Y.-K., Levinthal, F., Levinthal, C. & Hubbell, W. L. Science 259, 960–963 (1993).

    Article  CAS  Google Scholar 

  25. Thorgeirsson, T. E. et al. J. Mol. Biol. 273, 951–957 (1997).

    Article  CAS  Google Scholar 

  26. Brennwald, P. et al. Cell 79, 245–258 (1994).

    Article  CAS  Google Scholar 

  27. Guan, K. & Dixon, J. E. Anal. Biochem. 192, 262–267 (1991).

    Article  CAS  Google Scholar 

  28. Calakos, N., Bennett, M. K., Peterson, K. E. & Scheller, R. H. Science 263, 1146–1149 (1994).

    Article  CAS  Google Scholar 

  29. Cormack, B. In Current Protocols in Molecular Biology (eds Ausubel, F. M. et al. ) 8.5.1–8.5.10 (John Wiley & Sons, Inc., New York; 1997).

    Google Scholar 

  30. Bennett, M. K., Miller, K. G. & Scheller, R. H. J. Neurosci. 13, 1701–1707 (1993).

    Article  CAS  Google Scholar 

  31. Harbury, P. B., Zhang, T., Kim, P. S. & Alber, T. Science 262, 1401–1407 (1993).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank L. Gonzalez, Jr. for helpful discussions throughout this work. Support for this research was provided by the National Institutes of Health (M.K.B. and Y.-K.S.), the McKnight Fund for Neuroscience (M.K.B.), and a Searle Scholarship (Y.-K.S.).

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Correspondence to Mark K. Bennett.

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Poirier, M., Xiao, W., Macosko, J. et al. The synaptic SNARE complex is a parallel four-stranded helical bundle. Nat Struct Mol Biol 5, 765–769 (1998). https://doi.org/10.1038/1799

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