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 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.
Giraudo
Claudio G
CG
Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, 1150 Saint Nicholas Avenue, Russ Berrie Building, Room 520, New York, NY 10032, USA. claudio.giraudo@yale.edu
Garcia-Diaz
Alejandro
A
Eng
William S
WS
Chen
Yuhang
Y
Hendrickson
Wayne A
WA
Melia
Thomas J
TJ
Rothman
James E
JE
D033942:Adaptor Proteins, Vesicular Transport; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008561:Membrane Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D050600:SNARE Proteins / Q000737:chemistry* / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000737:chemistry* / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; D050988:Vesicle-Associated Membrane Protein 2; C095992:complexin I