3-DIMENSIONAL STRUCTURE OF AN EVOLUTIONARILY CONSERVED N-TERMINAL DOMAIN OF SYNTAXIN 1A

Syntaxin 1A plays a central role in neurotransmitter release through m ultiple protein-protein interactions. We have used NMR spectroscopy to identify an autonomously folded N-terminal domain in syntaxin 1A and to elucidate its three-dimensional structure. This 120-residue N-termi nal domain is conserved in plasma membrane syntaxins but not in other syntaxins, indicating a specific role in exocytosis. The domain contai ns three long or helices that form an up-and-down bundle with a left-h anded twist. A striking residue conservation is observed throughout a long groove that is likely to provide a specific surface for protein-p rotein interactions. A highly acidic region binds to the C(2)A domain of synaptotagmin I in a Ca2+-dependent interaction that may serve as a n electrostatic switch in neurotransmitter release.