Volume 548 Issue 7668, 24 August 2017

Rapid triggering of neurotransmitter release by action potentials requires that synaptic vesicles are primed for fast fusion with the presynaptic membrane, but the molecular basis of vesicle priming has been unclear. An interaction between the SNARE complex and the protein synaptotagmin-1 has already been identified as part of the process. In this week’s issue, Axel Brunger and colleagues complete the picture with crystal structures of a primed pre-fusion complex consisting of the SNARE complex (green, red and blue) and the protein complexin (yellow) and a second synaptotagmin-1 molecule (violet). This complex includes a newly revealed tripartite SNARE–complexin–synaptotagmin-1 interface that primes and locks the complex ready for action. Action-potential-driven calcium ions bind to the two synaptotagmin-1 proteins to unlock the complex and trigger membrane fusion on a sub-millisecond timescale. Cover image: Eric Smith, Jeremy Leitz and Qiangjun Zhou

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