How SNARE molecules mediate membrane fusion: recent insights from molecular simulations.

SNARE molecules are the core constituents of the protein machinery that facilitate fusion of synaptic vesicles with the presynaptic plasma membrane, resulting in the release of neurotransmitter. On a molecular level, SNARE complexes seem to play a quite versatile and involved role during all stages of fusion. In addition to merely triggering fusion by forcing the opposing membranes into close proximity, SNARE complexes are now seen to also overcome subsequent fusion barriers and to actively guide the fusion reaction up to the expansion of the fusion pore. Here, we review recent advances in the understanding of SNARE-mediated membrane fusion by molecular simulations.

[1]  J. Hoh,et al.  Splaying of aliphatic tails plays a central role in barrier crossing during liposome fusion. , 2010, The journal of physical chemistry. B.

[2]  M. Schick,et al.  Dependence of the energies of fusion on the intermembrane separation: optimal and constrained. , 2007, The Journal of chemical physics.

[3]  D. Tieleman,et al.  The MARTINI force field: coarse grained model for biomolecular simulations. , 2007, The journal of physical chemistry. B.

[4]  H. Grubmüller,et al.  Caught in the Act: Visualization of SNARE‐Mediated Fusion Events in Molecular Detail , 2011, Chembiochem : a European journal of chemical biology.

[5]  T. Salditt,et al.  Membrane fusion intermediates and the effect of cholesterol: An in-house X-ray scattering study , 2009, The European physical journal. E, Soft matter.

[6]  Reinhard Jahn,et al.  Helical extension of the neuronal SNARE complex into the membrane , 2009, Nature.

[7]  Peter M. Kasson,et al.  Ensemble molecular dynamics yields submillisecond kinetics and intermediates of membrane fusion , 2006, Proceedings of the National Academy of Sciences.

[8]  Yonathan Kozlovsky,et al.  Lipid intermediates in membrane fusion: formation, structure, and decay of hemifusion diaphragm. , 2002, Biophysical journal.

[9]  M. Müller,et al.  A new mechanism of model membrane fusion determined from Monte Carlo simulation. , 2002, Biophysical journal.

[10]  M. Mueller,et al.  Field theoretic study of bilayer membrane fusion: II. Mechanism of a stalk-hole complex. , 2005, Biophysical journal.

[11]  A. Herrmann,et al.  Direct visualization of large and protein-free hemifusion diaphragms. , 2009, Biophysical journal.

[12]  Mathias W. Hofmann,et al.  Self-interaction of a SNARE transmembrane domain promotes the hemifusion-to-fusion transition. , 2006, Journal of molecular biology.

[13]  M. Lafleur,et al.  Polymorphism of POPE/cholesterol system: a 2H nuclear magnetic resonance and infrared spectroscopic investigation. , 1998, Biophysical journal.

[14]  M. Kozlov,et al.  Protein-lipid interplay in fusion and fission of biological membranes. , 2003, Annual review of biochemistry.

[15]  A. Mark,et al.  Phase behavior of a phospholipid/fatty acid/water mixture studied in atomic detail. , 2006, Journal of the American Chemical Society.

[16]  J. Shillcock,et al.  The fusion of membranes and vesicles: pathway and energy barriers from dissipative particle dynamics. , 2009, Biophysical journal.

[17]  A. J. Markvoort,et al.  A detailed look at vesicle fusion. , 2006, The journal of physical chemistry. B.

[18]  Huey W. Huang,et al.  A rhombohedral phase of lipid containing a membrane fusion intermediate structure. , 2003, Biophysical journal.

[19]  J. Rothman,et al.  Close Is Not Enough , 2000, The Journal of cell biology.

[20]  Helmut Grubmüller,et al.  Mechanical coupling via the membrane fusion SNARE protein syntaxin 1A: a molecular dynamics study. , 2003, Biophysical journal.

[21]  Reinhard Lipowsky,et al.  Tension-induced fusion of bilayer membranes and vesicles , 2005, Nature materials.

[22]  Marc Baaden,et al.  Coarse-grain simulations of the R-SNARE fusion protein in its membrane environment detect long-lived conformational sub-states. , 2009, Chemphyschem : a European journal of chemical physics and physical chemistry.

[23]  M. Kozlov,et al.  Mechanics of membrane fusion , 2008, Nature Structural &Molecular Biology.

[24]  A. Mark,et al.  Molecular view of hexagonal phase formation in phospholipid membranes. , 2004, Biophysical journal.

[25]  M. Schick Membrane Fusion: the Emergence of a New Paradigm , 2011 .

[26]  M. Schick,et al.  Calculation of free energy barriers to the fusion of small vesicles. , 2008, Biophysical journal.

[27]  K. Daoulas,et al.  Measuring excess free energies of self-assembled membrane structures. , 2010, Faraday discussions.

[28]  Reinhard Lipowsky,et al.  Solvent-exposed tails as prestalk transition states for membrane fusion at low hydration. , 2010, Journal of the American Chemical Society.

[29]  B. Davletov,et al.  Self-assembly of SNARE fusion proteins into star-shaped oligomers. , 2005, The Biochemical journal.

[30]  F. Wouters,et al.  One SNARE complex is sufficient for membrane fusion , 2010, Nature Structural &Molecular Biology.

[31]  M. Kozlov,et al.  Lipids in biological membrane fusion , 1995, The Journal of Membrane Biology.

[32]  E. Neher,et al.  Fast Vesicle Fusion in Living Cells Requires at Least Three SNARE Complexes , 2010, Science.

[33]  Reinhard Jahn,et al.  Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution , 1998, Nature.

[34]  Yonathan Kozlovsky,et al.  Stalk model of membrane fusion: solution of energy crisis. , 2002, Biophysical journal.

[35]  Peter M. Kasson,et al.  Atomic-Resolution Simulations Predict a Transition State for Vesicle Fusion Defined by Contact of a Few Lipid Tails , 2010, PLoS Comput. Biol..

[36]  Peter M. Kasson,et al.  Control of Membrane Fusion Mechanism by Lipid Composition: Predictions from Ensemble Molecular Dynamics , 2007, PLoS Comput. Biol..

[37]  T. Südhof Membrane fusion as a team effort , 2007, Proceedings of the National Academy of Sciences.

[38]  Marcus Mueller,et al.  Field theoretic study of bilayer membrane fusion , 2004 .

[39]  Helmut Grubmüller,et al.  Molecular Anatomy of a Trafficking Organelle , 2006, Cell.

[40]  R. Jahn,et al.  Dynamic structure of lipid-bound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation , 2009, Proceedings of the National Academy of Sciences.

[41]  H. Grubmüller,et al.  Line-Tension Controlled Mechanism for Influenza Fusion , 2012, PloS one.

[42]  J Y Lee,et al.  Field theoretic study of bilayer membrane fusion III: membranes with leaves of different composition. , 2007, Biophysical journal.

[43]  Thorsten Lang,et al.  Membrane fusion. , 2002, Current opinion in cell biology.

[44]  Benedikt Westermann,et al.  SNAREpins: Minimal Machinery for Membrane Fusion , 1998, Cell.

[45]  Reinhard Jahn,et al.  SNAREs — engines for membrane fusion , 2006, Nature Reviews Molecular Cell Biology.

[46]  V. Pande,et al.  Water ordering at membrane interfaces controls fusion dynamics. , 2011, Journal of the American Chemical Society.

[47]  R. Macdonald,et al.  Cholesterol stabilizes hemifused phospholipid bilayer vesicles. , 2001, Biochimica et biophysica acta.

[48]  F. W. Tse,et al.  Influence of Cholesterol on Catecholamine Release from the Fusion Pore of Large Dense Core Chromaffin Granules , 2010, The Journal of Neuroscience.

[49]  D. Bruns,et al.  v-SNARE Actions during Ca2+-Triggered Exocytosis , 2007, Cell.

[50]  Yen Sun,et al.  Adhesion and merging of lipid bilayers: a method for measuring the free energy of adhesion and hemifusion. , 2011, Biophysical journal.

[51]  E. Evans,et al.  Water permeability and mechanical strength of polyunsaturated lipid bilayers. , 2000, Biophysical journal.

[52]  D. Tieleman,et al.  Lung surfactant protein SP-B promotes formation of bilayer reservoirs from monolayer and lipid transfer between the interface and subphase. , 2011, Biophysical journal.

[53]  J. Freed,et al.  A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol , 2009, Proceedings of the National Academy of Sciences.

[54]  M. Mueller,et al.  Field theoretic study of bilayer membrane fusion. I. Hemifusion mechanism. , 2003, Biophysical journal.

[55]  D Needham,et al.  Elastic deformation and failure of lipid bilayer membranes containing cholesterol. , 1990, Biophysical journal.

[56]  A. J. Markvoort,et al.  Lipid acrobatics in the membrane fusion arena. , 2011, Current topics in membranes.

[57]  Siewert J Marrink,et al.  The mechanism of vesicle fusion as revealed by molecular dynamics simulations. , 2003, Journal of the American Chemical Society.

[58]  J. Rizo,et al.  SNARE-mediated lipid mixing depends on the physical state of the vesicles. , 2006, Biophysical journal.

[59]  M. Jackson,et al.  Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis , 2004, Science.

[60]  A. Brunger,et al.  Neuronal SNAREs do not trigger fusion between synthetic membranes but do promote PEG-mediated membrane fusion. , 2006, Biophysical journal.

[61]  Mathias W. Hofmann,et al.  The role of transmembrane domains in membrane fusion , 2007, Cellular and Molecular Life Sciences.

[62]  M. Lindau,et al.  The role of the C terminus of the SNARE protein SNAP-25 in fusion pore opening and a model for fusion pore mechanics , 2008, Proceedings of the National Academy of Sciences.

[63]  Reinhard Lipowsky,et al.  Pathway of membrane fusion with two tension-dependent energy barriers. , 2007, Physical review letters.

[64]  Dirk Fasshauer,et al.  Is Assembly of the SNARE Complex Enough to Fuel Membrane Fusion? , 2009, Journal of Biological Chemistry.

[65]  Marc Baaden,et al.  Interactions between neuronal fusion proteins explored by molecular dynamics. , 2008, Biophysical journal.

[66]  Hongxia Guo,et al.  Simulation study of protein-mediated vesicle fusion. , 2009, The journal of physical chemistry. B.

[67]  A T Brünger,et al.  Structural Changes Are Associated with Soluble N-Ethylmaleimide-sensitive Fusion Protein Attachment Protein Receptor Complex Formation* , 1997, The Journal of Biological Chemistry.

[68]  Alexander M. Walter,et al.  Role of the synaptobrevin C terminus in fusion pore formation , 2010, Proceedings of the National Academy of Sciences.

[69]  R. Larson,et al.  The MARTINI Coarse-Grained Force Field: Extension to Proteins. , 2008, Journal of chemical theory and computation.

[70]  Fan Zhang,et al.  Hemifusion in SNARE-mediated membrane fusion , 2005, Nature Structural &Molecular Biology.

[71]  L. Huang,et al.  pH-sensitive liposomes: acid-induced liposome fusion. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[72]  Avishay Efrat,et al.  Point-like protrusion as a prestalk intermediate in membrane fusion pathway. , 2007, Biophysical journal.

[73]  Lipid mixing and content release in single-vesicle, SNARE-driven fusion assay with 1-5 ms resolution. , 2009, Biophysical journal.

[74]  Thomas B Woolf,et al.  Insights into the molecular mechanism of membrane fusion from simulation: evidence for the association of splayed tails. , 2003, Physical review letters.