X-ray structure of a neuronal complexin-SNARE complex from squid.
Nerve terminals release neurotransmitters from vesicles into the synaptic cleft upon transient increases in intracellular Ca(2+). This exocytotic process requires the formation of trans SNARE complexes and is regulated by accessory proteins including the complexins. Here we report the crystal structure of a squid core complexin-SNARE complex at 2.95-A resolution. A helical segment of complexin binds in anti-parallel fashion to the four-helix bundle of the core SNARE complex and interacts at its C terminus with syntaxin and synaptobrevin around the ionic zero layer of the SNARE complex. We propose that this structure is part of a multiprotein fusion machinery that regulates vesicle fusion at a late pre-fusion stage. Accordingly, Ca(2+) may initiate membrane fusion by acting directly or indirectly on complexin, thus allowing the conformational transitions of the trans SNARE complex that are thought to drive membrane fusion.
Bracher
Andreas
A
European Molecular Biology Laboratory, 6 rue Jules Horowitz, 38042 Grenoble, France.
Kadlec
Jan
J
Betz
Heinrich
H
Weissenhorn
Winfried
W
D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling; D018360:Crystallography, X-Ray; D049832:Decapodiformes / Q000737:chemistry*; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008958:Models, Molecular; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D050600:SNARE Proteins; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D046911:Macromolecular Substances; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C095992:complexin I; C095993:complexin II