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Helical extension of the neuronal SNARE complex into the membrane

Nature volume 460, pages 525–528 (2009)Cite this article

Abstract

Neurotransmission relies on synaptic vesicles fusing with the membrane of nerve cells to release their neurotransmitter content into the synaptic cleft, a process requiring the assembly of several members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family. SNAREs represent an evolutionarily conserved protein family that mediates membrane fusion in the secretory and endocytic pathways of eukaryotic cells1,2,3. On membrane contact, these proteins assemble in trans between the membranes as a bundle of four α-helices, with the energy released during assembly being thought to drive fusion4,5,6. However, it is unclear how the energy is transferred to the membranes and whether assembly is conformationally linked to fusion. Here, we report the X-ray structure of the neuronal SNARE complex, consisting of rat syntaxin 1A, SNAP-25 and synaptobrevin 2, with the carboxy-terminal linkers and transmembrane regions at 3.4 Å resolution. The structure shows that assembly proceeds beyond the already known core SNARE complex7, resulting in a continuous helical bundle that is further stabilized by side-chain interactions in the linker region. Our results suggest that the final phase of SNARE assembly is directly coupled to membrane merger.

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Figure 1: Linkers and transmembrane regions add stability to SNARE complexes.
Figure 2: Synaptobrevin 2 and syntaxin 1A form continuous helices.
Figure 3: An aromatic layer appears to be crucial for linker contact.
Figure 4: Model of the synaptic SNARE complex inserted in a membrane.

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Acknowledgements

We thank U. Ries for technical assistance, C. Kutzner and H. Grubmüller for providing the model shown in Fig. 4, R. Lührmann for access to his X-ray facilities, D. Fasshauer and N. Pavlos for comments on the manuscript, W. Antonin for providing the expression constructs of endosomal SNAREs and the staff of beamlines PX1 and PX2 of the Swiss Light Source for support during diffraction data collection.

Author Contributions A.S. and R.J. planned the project, A.S. performed the experiments, A.S., G.W. and M.C.W. analysed the data and A.S. and R.J. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Authors and Affiliations

  1. Department of Neurobiology,,

    Alexander Stein & Reinhard Jahn

  2. Research Group X-ray Crystallography, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany ,

    Gert Weber & Markus C. Wahl

  3. Freie Universität Berlin, Fachbereich Biologie, Chemie, Pharmazie, Institut für Chemie und Biochemie, AG Strukturbiochemie, Takustraße 6, D-14195 Berlin, Germany ,

    Gert Weber & Markus C. Wahl

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Correspondence to Reinhard Jahn.

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Stein, A., Weber, G., Wahl, M. et al. Helical extension of the neuronal SNARE complex into the membrane. Nature 460, 525–528 (2009). https://doi.org/10.1038/nature08156

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