title: Dynamic structure of lipid-bound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation.
abstract: The synaptic vesicle protein synaptobrevin engages with syntaxin and SNAP-25 to form the SNARE complex, which drives membrane fusion in neuronal exocytosis. In the SNARE complex, the SNARE motif of synaptobrevin forms a 55-residue helix, but it has been assumed to be mostly unstructured in its prefusion form. NMR data for full-length synaptobrevin in dodecylphosphocholine micelles reveals two transient helical segments flanked by natively disordered regions and a third more stable helix. Transient helix I comprises the most N-terminal part of the SNARE motif, transient helix II extends the SNARE motif into the juxtamembrane region, and the more stable helix III is the transmembrane domain. These helices may have important consequences for SNARE complex folding and fusion: helix I likely forms a nucleation site, the C-terminal disordered SNARE motif may act as a folding arrest signal, and helix II likely couples SNARE complex folding and fusion.
authors.affiliation: Biomolecular Magnetic Resonance Research Core, PO Box 800741, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Ellena
authors.forename: Binyong
authors.initials: B
authors.lastname: Liang
authors.forename: Maciej
authors.initials: M
authors.lastname: Wiktor
authors.forename: Alexander
authors.initials: A
authors.lastname: Stein
authors.forename: David S
authors.initials: DS
authors.lastname: Cafiso
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
authors.forename: Lukas K
authors.initials: LK
authors.lastname: Tamm
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D009474:Neurons / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D050683:R-SNARE Proteins / Q000737:chemistry*; D051381:Rats; D050600:SNARE Proteins / Q000737:chemistry*
chemical_list: D008823:Micelles; D050683:R-SNARE Proteins; D050600:SNARE Proteins