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Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution

Nature volume 395, pages 347–353 (1998)Cite this article

Abstract

The evolutionarily conserved SNARE proteins and their complexes are involved in the fusion of vesicles with their target membranes; however, the overall organization and structural details of these complexes are unknown. Here we report the X-ray crystal structure at 2.4 Å resolution of a core synaptic fusion complex containing syntaxin-1A, synaptobrevin-II and SNAP-25B. The structure reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion proteins. Conserved leucine-zipper-like layers are found at the centre of the synaptic fusion complex. Embedded within these leucine-zipper layers is an ionic layer consisting of an arginine and three glutamine residues contributed from each of the four α-helices. These residues are highly conserved across the entire SNARE family. The regions flanking the leucine-zipper-like layers contain a hydrophobic core similar to that of more general four-helix-bundle proteins. The surface of the synaptic fusion complex is highly grooved and possesses distinct hydrophilic, hydrophobic and charged regions. These characteristics may be important for membrane fusion and for the binding of regulatory factors affecting neurotransmission.

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Figure 1: Electron-density map of the synaptic fusion complex obtained by multi-MAD phasing, showing a methionine cluster.
Figure 2: Topology and organization of the synaptic fusion complex.
Figure 3: Ionic ‘0’ layer of the synaptic fusion complex.
Figure 4: Close-up view of the loop involving Sn2 at the C-terminal end of the synaptic fusion complex.
Figure 5: Hypothetical model of the synaptic fusion complex as it joins two membranes, and location of neurotoxin-mediated cleavage sites.
Figure 6: Surface plot showing the electrostatic potential of the synaptic fusion complex.

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Acknowledgements

We thank P. D. Adams and C. Ostermeier for advice; D. M. Engelman, K. M. Fiebig, T. Simonson and R. C. Yu for stimulating discussions; H. Bellamy for assistance with data collection at SSRL 1-5 (SSRL is funded by the Department of Energy; the SSRL Biotechnology Program is supported by the NIH; further SSRL support is provided by the Department of Energy); A. Joachimiak and staff at the Structural Biology Center at the Advanced Photon Source for assistance with data collection at 19ID (this national user facility is supported by the Department of Energy); L. Esser for assistance in figure preparation; and J. Pflugrath for help with d*TREK. This work was supported by the NIH (A.T.B.).

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Authors and Affiliations

  1. The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 06520, Connecticut, USA

    R. Bryan Sutton & Axel T. Brunger

  2. Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, D-37077, Germany

    Dirk Fasshauer & Reinhard Jahn

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  1. R. Bryan Sutton
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Correspondence to Axel T. Brunger.

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Sutton, R., Fasshauer, D., Jahn, R. et al. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution. Nature 395, 347–353 (1998). https://doi.org/10.1038/26412

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