Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs.

SNARE [soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein receptor] proteins are essential for membrane fusion and are conserved from yeast to humans. Sequence alignments of the most conserved regions were mapped onto the recently solved crystal structure of the heterotrimeric synaptic fusion complex. The association of the four alpha-helices in the synaptic fusion complex structure produces highly conserved layers of interacting amino acid side chains in the center of the four-helix bundle. Mutations in these layers reduce complex stability and cause defects in membrane traffic even in distantly related SNAREs. When syntaxin-4 is modeled into the synaptic fusion complex as a replacement of syntaxin-1A, no major steric clashes arise and the most variable amino acids localize to the outer surface of the complex. We conclude that the main structural features of the neuronal complex are highly conserved during evolution. On the basis of these features we have reclassified SNARE proteins into Q-SNAREs and R-SNAREs, and we propose that fusion-competent SNARE complexes generally consist of four-helix bundles composed of three Q-SNAREs and one R-SNARE.

[1]  T. Weimbs,et al.  A model for structural similarity between different SNARE complexes based on sequence relationships. , 1998, Trends in cell biology.

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

[3]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[4]  R. Scheller,et al.  Tomosyn Binds t-SNARE Proteins via a VAMP-like Coiled Coil , 1998, Neuron.

[5]  P. S. Kim,et al.  A buried polar interaction can direct the relative orientation of helices in a coiled coil. , 1998, Biochemistry.

[6]  H. Pelham,et al.  SNAREs and membrane fusion in the Golgi apparatus. , 1998, Biochimica et biophysica acta.

[7]  S. D. Carlson,et al.  Temperature-Sensitive Paralytic Mutations Demonstrate that Synaptic Exocytosis Requires SNARE Complex Assembly and Disassembly , 1998, Neuron.

[8]  A. T. Brunger,et al.  Identification of a minimal core of the synaptic SNARE complex sufficient for reversible assembly and disassembly. , 1998, Biochemistry.

[9]  Tao Xu,et al.  Multiple kinetic components of exocytosis distinguished by neurotoxin sensitivity , 1998, Nature Neuroscience.

[10]  W. Wickner,et al.  Vam7p, a vacuolar SNAP‐25 homolog, is required for SNARE complex integrity and vacuole docking and fusion , 1998, The EMBO journal.

[11]  P. Haydon,et al.  Modulation of an early step in the secretory machinery in hippocampal nerve terminals. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Götte,et al.  A new beat for the SNARE drum. , 1998, Trends in cell biology.

[13]  M. Nonet,et al.  The Caenorhabditis elegans unc-64 locus encodes a syntaxin that interacts genetically with synaptobrevin. , 1998, Molecular biology of the cell.

[14]  Akira Mizoguchi,et al.  Tomosyn: a Syntaxin-1–Binding Protein that Forms a Novel Complex in the Neurotransmitter Release Process , 1998, Neuron.

[15]  T. Stevens,et al.  A Human Homolog Can Functionally Replace the Yeast Vesicle-associated SNARE Vti1p in Two Vesicle Transport Pathways* , 1998, The Journal of Biological Chemistry.

[16]  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.

[17]  B. Gähwiler,et al.  Ca2+ or Sr2+ Partially Rescues Synaptic Transmission in Hippocampal Cultures Treated with Botulinum Toxin A and C, But Not Tetanus Toxin , 1997, The Journal of Neuroscience.

[18]  A. Brünger,et al.  Analysis of a Yeast SNARE Complex Reveals Remarkable Similarity to the Neuronal SNARE Complex and a Novel Function for the C Terminus of the SNAP-25 Homolog, Sec9* , 1997, The Journal of Biological Chemistry.

[19]  P. Hanson,et al.  Neurotransmitter release — four years of SNARE complexes , 1997, Current Opinion in Neurobiology.

[20]  R M Esnouf,et al.  An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. , 1997, Journal of molecular graphics & modelling.

[21]  R. Kelly,et al.  Effect of Mutations in Vesicle-Associated Membrane Protein (VAMP) on the Assembly of Multimeric Protein Complexes , 1997, The Journal of Neuroscience.

[22]  A. Brünger,et al.  A Structural Change Occurs upon Binding of Syntaxin to SNAP-25* , 1997, The Journal of Biological Chemistry.

[23]  B. Dasgupta,et al.  N-Ethylmaleimide-sensitive Factor Acts at a Prefusion ATP-dependent Step in Ca2+-activated Exocytosis* , 1996, The Journal of Biological Chemistry.

[24]  M. Gerstein,et al.  Average core structures and variability measures for protein families: application to the immunoglobulins. , 1995, Journal of molecular biology.

[25]  Thomas C. Südhof,et al.  The synaptic vesicle cycle: a cascade of protein–protein interactions , 1995, Nature.

[26]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[27]  J. Rothman,et al.  Mechanisms of intracellular protein transport , 1994, Nature.

[28]  T. Südhof,et al.  Synaptic vesicle membrane fusion complex: action of clostridial neurotoxins on assembly. , 1994, The EMBO journal.

[29]  P. Brennwald,et al.  Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in exocytosis , 1994, Cell.

[30]  R. Jahn,et al.  Molecular Mechanisms of Clostridial Neurotoxins , 1994, Annals of the New York Academy of Sciences.

[31]  Jonathan Pevsner,et al.  Specificity and regulation of a synaptic vesicle docking complex , 1994, Neuron.

[32]  Reinhard Jahn,et al.  Vesicle fusion from yeast to man , 1994, Nature.

[33]  S. Ferro-Novick,et al.  Bos1p, an integral membrane protein of the endoplasmic reticulum to Golgi transport vesicles, is required for their fusion competence , 1993, Cell.

[34]  Paul Tempst,et al.  SNAP receptors implicated in vesicle targeting and fusion , 1993, Nature.

[35]  D. Gallwitz,et al.  The yeast SLY gene products, suppressors of defects in the essential GTP-binding Ypt1 protein, may act in endoplasmic reticulum-to-Golgi transport , 1991, Molecular and cellular biology.

[36]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[37]  R. Schekman,et al.  Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway , 1980, Cell.

[38]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.