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Alternative zippering as an on-off switch for SNARE-mediated fusion.

ABSTRACT: 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.

SUBMITTER: Giraudo CG

PROVIDER: S-EPMC3736854 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Alternative zippering as an on-off switch for SNARE-mediated fusion.

Giraudo Claudio G CG Garcia-Diaz Alejandro A Eng William S WS Chen Yuhang Y Hendrickson Wayne A WA Melia Thomas J TJ Rothman James E JE

Science (New York, N.Y.) 20090101 5913

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 com ...[more]

PMID: 19164750

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