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Nature 460, 525-528 (23 July 2009) | doi:10.1038/nature08156; Received 26 January 2009; Accepted 15 May 2009; Published online 1 July 2009

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Helical extension of the neuronal SNARE complex into the membrane

Alexander Stein1, Gert Weber2,3, Markus C. Wahl2,3 & Reinhard Jahn1

  1. Department of Neurobiology,
  2. Research Group X-ray Crystallography, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany
  3. Freie Universität Berlin, Fachbereich Biologie, Chemie, Pharmazie, Institut für Chemie und Biochemie, AG Strukturbiochemie, Takustras zlige 6, D-14195 Berlin, Germany

Correspondence to: Reinhard Jahn1 Correspondence and requests for materials should be addressed to R.J. (Email: rjahn@gwdg.de).

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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 alpha-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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