Travis J Eisemann, Frederick Allen ... Frederick M Hughson
Whereas in a paradigmatic structure an SM protein chaperone clamps its client SNARE shut, a second structure demonstrates that an SM protein can also hold its SNARE open to promote assembly.
During neurotransmitter release, calcium-induced membrane insertion of the C2B domain of Synaptotagmin re-orients the bound SNARE complex which dilates the fusion pore in a mechanical lever action.
Braden T Lobingier, Daniel P Nickerson ... Alexey J Merz
Sec1/Munc18 (SM) proteins shield SNARE complexes from NSF/Sec18-mediated disassembly through cooperative binding interactions with SNARE complexes and the universal co-chaperone α-SNAP/Sec17.
A few SNARE complexes suffice to fuse membranes, but many more are needed to dilate the nascent fusion pore by molecular crowding for efficient neurotransmitter or hormone release during exocytosis.
Daniëlle Rianne José Verboogen, Natalia González Mancha ... Geert van den Bogaart
A novel microscopy-based assay shows that dendritic cells encountering pathogenic stimuli form increased complexes of specific SNARE proteins, driving release of large amounts of inflammatory cytokines.
Electron-cryomicroscopy structures of the supercomplex of NSF, αSNAP, and neuronal SNAREs in the presence of ATP under non-hydrolyzing conditions at 3.9 Å resolution reveal interactions between the N-terminal residues of SNAP-25 and NSF.
The Munc18-1 protein promotes formation of the t-SNARE complex and the half-zippered SNARE complex, two rate-limiting steps of SNARE assembly, to enhance membrane fusion.
NSF is part of a membrane trafficking quality control system that disassembles both properly formed and off-pathway SNARE complexes, and the disassembly activity may be regulated by complexin.