X-ray Structure of a Neuronal Complexin-SNARE Complex from Squid

• Published in: The Journal of biological chemistry Vol. 277; no. 29; pp. 26517 - 26523
• Main Authors: Bracher, Andreas, Kadlec, Jan, Betz, Heinrich, Weissenhorn, Winfried
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.07.2002; American Society for Biochemistry and Molecular Biology
• Subjects: Adaptor Proteins, Vesicular Transport; Amino Acid Sequence; Animals; Calcium Signaling; Crystallography, X-Ray; Decapodiformes - chemistry; Macromolecular Substances; Membrane Proteins; Models, Molecular; Multiprotein Complexes; Nerve Tissue Proteins; Protein Conformation; Protein Structure, Secondary; Sequence Alignment; SNARE Proteins; Vesicular Transport Proteins
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M203460200

Nerve terminals release neurotransmitters from vesicles into the synaptic cleft upon transient increases in intracellular Ca2+. 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-Å 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, Ca2+ 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.