Munc18-1 binds directly to the neuronal SNARE complex

Irina Dulubova, Mikhail Khvotchev, Siqi Liu, Iryna Huryeva, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


Both SM proteins (for Sec1/Munc18-like proteins) and SNARE proteins (for soluble NSF-attachment protein receptors) are essential for intracellular membrane fusion, but the general mechanism of coupling between their functions is unclear, in part because diverse SM protein/SNARE binding modes have been described. During synaptic vesicle exocytosis, the SM protein Munc18-1 is known to bind tightly to the SNARE protein syntaxin-1, but only when syntaxin-1 is in a closed conformation that is incompatible with SNARE complex formation. We now show that Munc18-1 also binds tightly to assembled SNARE complexes containing syntaxin-1. The newly discovered Munc18-1/SNARE complex interaction involves contacts of Munc18-1 with the N-terminal Habc domain of syntaxin-1 and the four-helical bundle of the assembled SNARE complex. Together with earlier studies, our results suggest that binding of Munc18-1 to closed syntaxin-1 is a specialization that evolved to meet the strict regulatory requirements of neuronal exocytosis, whereas binding of Mund8-1 to assembled SNARE complexes reflects a general function of SM proteins involved in executing membrane fusion.

Original languageEnglish (US)
Pages (from-to)2697-2702
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 20 2007


  • Membrane fusion
  • Neurotransmitter release
  • Sec1/Munc18-like proteins
  • Synapse
  • Zexocytosis

ASJC Scopus subject areas

  • General


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