Alternative Zippering as an On-Off Switch for SNARE-Mediated Fusion

Membrane fusion between vesicles and target membranes involves the zippering of a four-helix bundle generated by constituent helices derived from target- and vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). In neurons, the protein complexin clamps otherwise sp...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) 2009-01, Vol.323 (5913), p.512-516
Main Authors:	Giraudo, Claudio G, Garcia-Diaz, Alejandro, Eng, William S, Chen, Yuhang, Hendrickson, Wayne A, Melia, Thomas J, Rothman, James E
Format:	Article
Language:	eng
Subjects:	Adaptor Proteins, Vesicular Transport Amino Acid Motifs Amino Acid Sequence Amino acids Calcium Cell fusion Cellular biology Evolutionary linguistics HeLa Cells Humans Hydrophobic and Hydrophilic Interactions Intracellular membranes Membrane Fusion Membranes Models, Molecular Molecular biology Molecular Sequence Data Mutant Proteins - chemistry Mutant Proteins - metabolism Mutation Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neurons Neurosciences Neurotransmitters Protein Binding Protein Structure, Secondary Proteins Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - metabolism SNARE proteins SNARE Proteins - chemistry SNARE Proteins - metabolism Toxins Vesicle-Associated Membrane Protein 2 - chemistry Vesicle-Associated Membrane Protein 2 - metabolism
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Summary:	Membrane fusion between vesicles and target membranes involves the zippering of a four-helix bundle generated by constituent helices derived from target- and vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). In neurons, the protein complexin clamps otherwise spontaneous fusion by SNARE proteins, allowing neurotransmitters and other mediators to be secreted when and where they are needed as this clamp is released. The membrane-proximal accessory helix of complexin is necessary for clamping, but its mechanism of action is unknown. Here, we present experiments using a reconstituted fusion system that suggest a simple model in which the complexin accessory helix forms an alternative four-helix bundle with the target-SNARE near the membrane, preventing the vesicle-SNARE from completing its zippering.
ISSN:	0036-8075 1095-9203