publications

Tomosyn binds t-SNARE proteins via a VAMP-like coiled coil

Masuda ES, Huang BC, Fisher JM, Luo Y, Scheller RH.

Neuron 1998 Sep;21(3):479-80.

We have started, among several approaches, to search for proteins that interact with SNARE proteins from mast cells using a yeast two-hybrid system in order to identify and map regulatory components of the exocytic process. Initial results showed us that a new syntaxin1-binding protein, tomosyn, has the capacity to bind not only syntaxin-1a but also syntaxin-4 and SNAP-23. We defined the carboxy-terminal 82 amino-acid residues of tomosyn as the domain that interacts with the coiled-coil domains of syntaxin and SNAP-23. On closer inspection, this domain was found to encode a predicted coiled coil that was related to the VAMP-like coiled coil sequences. This finding thus argues that tomosyn, like VAMP proteins, is capable of forming trimeric complexes with t-SNAREs and is consistent with the proposed replacement of tomosyn by VAMP during the exocytic process. We propose that tomosyn is the first of a class of membrane trafficking regulators which utilizes a SNARE coil domain to substitute for one of the components of the four-helix bundle that makes up the core complex. Further characterization of the tomosyn molecule should shed light on the regulation of dissociation and association of SNARE complexes during the exocytic membrane fusion events.