Vam3p structure reveals conserved and divergent properties of syntaxins

Syntaxins and Sec1/munc18 proteins are central to intracellular membrane fu sion. All syntaxins comprise a variable N-terminal region, a conserved SNAR E motif that is critical for SNARE complex formation, and a transmembrane r egion. The N-terminal region of neuronal syntaxin 1A contains a three-helix domain that folds back onto the SNARE motif forming a 'closed' conformatio n; this conformation is required for munc18-1 binding. We have examined the generality of the structural properties of syntaxins by NMR analysis of Va m3p, a yeast syntaxin essential for vacuolar fusion, Surprisingly, Vam3p al so has an N-terminal three-helical domain despite lacking apparent sequence homology with syntaxin 1A in this region. However, Vam3p does not form a c losed conformation and its N-terminal domain is not required for binding to the Sec1/munc18 protein Vps33p, suggesting that critical distinctions exis t in the mechanisms used by syntaxins to govern different types of membrane fusion.