Fakultät für Chemie - Biochemistry III
Uni von A-Z
Bielefeld University > Department of Chemistry > Research Groups > Prof. Dr. Gabriele Fischer von Mollard > Biochemistry III
Proc. Natl. Acad. Sci. USA doi/10.1073/pnas.1013101108 (2011)

ENTH domains bind on opposite sides of two SNAREs.

Wang, J., Gossing, M., Fang, P., Zimmermann, J., Li, X., Fischer von Mollard, G.*, Niu, L.*, Teng, M.*

* corresponding authors

Sets of SNARE proteins mediate membrane fusion by assembling into core complexes. Multiple SNAREs are thought to function in different intracellular trafficking steps but it is often unclear which of the SNAREs cooperate in individual fusion reactions. Here we report that syntaxin 7, syntaxin 8, vti1b, and endobrevin/VAMP-8 form a complex that functions in the fusion of late endosomes/lysosomes. Antibodies specific for each of the proteins coprecipitate the complex, inhibit homotypic fusion of late endosomes in vitro, and retard delivery of endocytosed epidermal growth factor to lysosomes. The purified proteins form core complexes with biochemical and biophysical properties remarkably similar to the neuronal core complex although each of the four proteins carries a transmembrane domain, and three have independently folded N-terminal domains. Substitution experiments in combination with sequence and structural comparisons revealed that each protein occupies an unique position in the complex, with syntaxin 7 corresponding to syntaxin 1, and vti1b and syntaxin 8 corresponding to the N- and C-terminal domains of SNAP-25, respectively. We conclude that structure of core complexes and thus their molecular mechanism in membrane fusion is highly conserved between distant SNAREs.