title: Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A.
abstract: Syntaxin 1A plays a central role in neurotransmitter release through multiple 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-terminal domain is conserved in plasma membrane syntaxins but not in other syntaxins, indicating a specific role in exocytosis. The domain contains three long alpha helices that form an up-and-down bundle with a left-handed twist. A striking residue conservation is observed throughout a long groove that is likely to provide a specific surface for protein-protein interactions. A highly acidic region binds to the C2A domain of synaptotagmin I in a Ca2+-dependent interaction that may serve as an electrostatic switch in neurotransmitter release.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: I
authors.initials: I
authors.lastname: Fernandez
authors.forename: J
authors.initials: J
authors.lastname: Ubach
authors.forename: I
authors.initials: I
authors.lastname: Dulubova
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: J
authors.initials: J
authors.lastname: Rizo
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D009682:Magnetic Resonance Spectroscopy; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000502:physiology; D050863:Synaptotagmin I; D050857:Synaptotagmins; D050827:Syntaxin 1
chemical_list: D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C494213:Stx1a protein, rat; D050863:Synaptotagmin I; D050827:Syntaxin 1; C494312:Syt1 protein, rat; D050857:Synaptotagmins; D002118:Calcium