A role of complexin-lipid interactions in membrane fusion

Complexins (Cpxs) and synaptotagmins regulate calcium-dependent exocytosis. A central helix in Cpx confers specific binding to the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) fusion machinery. An accessory helix in the amino-terminal region inhibits membrane fusion by blocking SNAREpin zippering. We now show that an amphipathic helix in the carboxy-terminal region of CpxI binds lipid bilayers and affects SNARE-mediated lipid mixing in a liposome fusion assay. The substitution of a hydrophobic amino acid within the helix by a charged residue abolishes the lipid interaction and the stimulatory effect of CpxI in liposome fusion. In contrast, the introduction of the bulky hydrophobic amino acid tryptophan stimulates lipid binding and liposome fusion. This data shows that local Cpx-lipid interactions can play a role in membrane fusion.