ArticleProceedings of the National Academy of Sciences of the United States of America2019
Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.Molecular neurodegeneration · 2025Review
- Using multiscale molecular dynamics simulations to explore the fusion machinery underlying neurotransmitter release.Quarterly reviews of biophysics · 2025Review
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
- Membrane Association of Intrinsically Disordered Proteins.Annual review of biophysics · 2025Review
- Functionally distinct SNARE motifs of SNAP25 cooperate in SNARE assembly and membrane fusion.Biophysical journal · 2025Article
- Predicting the sequence-dependent backbone dynamics of intrinsically disordered proteins.eLife · 2024Article
- Predicting the Sequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins.bioRxiv : the preprint server for biology · 2024Article
- Mechanisms of SNARE proteins in membrane fusion.Nature reviews. Molecular cell biology · 2024Review
- EHD2 regulates plasma membrane integrity and downstream insulin receptor signaling events.Molecular biology of the cell · 2023Article
- Mass spectrometry uncovers intermediates and off-pathway complexes for SNARE complex assembly.Communications biology · 2023Article
- SNARE Proteins in Synaptic Vesicle Fusion.Advances in neurobiology · 2023Article
- Dark peptide discs for the investigation of membrane proteins in supported lipid bilayers: the case of synaptobrevin 2 (VAMP2).Nanoscale advances · 2022Article
- ReSMAP: Web Server for Predicting Residue-Specific Membrane-Association Propensities of Intrinsically Disordered Proteins.Membranes · 2022Article
- The function of VAMP2 in mediating membrane fusion: An overview.Frontiers in molecular neuroscience · 2022Review
- NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications.Chemical Society reviews · 2021Review
- Chaperoning SNARE Folding and Assembly.Annual review of biochemistry · 2021Review
- Cross-linking mass spectrometry uncovers protein interactions and functional assemblies in synaptic vesicle membranes.Nature communications · 2021Article
- Calcium-Lipid Interactions Observed with Isotope-Edited Infrared Spectroscopy.Biophysical journal · 2020Article
- Recent Insights into Beta-cell Exocytosis in Type 2 Diabetes.Journal of molecular biology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Intrinsically disordered proteins (IDPs) and their conformational transitions play an important role in neurotransmitter release at the neuronal synapse. Here, the SNARE proteins are essential by forming the SNARE complex that drives vesicular membrane fusion. While it is widely accepted that the SNARE proteins are intrinsically disordered in their monomeric prefusion form, important mechanistic aspects of this prefusion conformation and its lipid interactions, before forming the SNARE complex, are not fully understood at the molecular level and remain controversial. Here, by a combination of NMR and fluorescence spectroscopy methods, we find that vesicular synaptobrevin-2 (syb-2) in its monomeric prefusion conformation shows high flexibility, characteristic for an IDP, but also a high dynamic range and increasing rigidity from the N to C terminus. The gradual increase in rigidity correlates with an increase in lipid binding affinity from the N to C terminus. It could also explain the increased rate for C-terminal SNARE zippering, known to be faster than N-terminal SNARE zippering. Also, the syb-2 SNARE motif and, in particular, the linker domain show transient and weak membrane binding, characterized by a high off-rate and low (millimolar) affinity. The transient membrane binding of syb-2 may compensate for the repulsive forces between the two membranes and/or the SNARE motifs and the membranes, helping to destabilize the hydrophilic-hydrophobic boundary in the bilayer. Therefore, we propose that optimum flexibility and membrane binding of syb-2 regulate SNARE assembly and minimize repulsive forces during membrane fusion.
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Registered trials
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