 SNARE Domain | |
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Structure:
 The three-dimensional crystal structure of a core heterotrimeric synaptic fusion complex containing syntaxin-1A (red), synaptobrevin-II (blue), and SNAP-25B (green) in a 1:1:1 stoichiometry has been solved and is depicted here. The structure reveals a highly twisted parallel four-helix bundle with a left-handed super-helical pitch. Leucine zipper-like layers appear to mediate the super-helical arrangement. Most of the binding energy of the SNARE complex comes from hydrophobic and ionic core packing interactions. Interactions in the core of the bundle are mostly hydrophobic, resembling that of other coiled-coil structures. Interestingly there is an ionic layer formed in the center of the four-helix bundles. The amino acids that contribute to this ionic layer are the most highly conserved residues among the SNARE superfamily. The peptide backbone of the super-helical structure forms a seal around the ionic core shielding it from the outside environment. The surface of the helical bundle is highly grooved and possesses distinct hydrophilic, hydrophobic, and charged regions that could play a role in mediating the specificity of membrane fusion and/or its regulation.
Structure Reference:
Sutton, RB. et al. (1998) Nature. 395(6700): 347-353. PDB: 1SFC.
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Domain binding and function:
 While the mechanism by which a vesicle fuses with its proper membrane target is poorly understood, it appears to involve a highly conserved set of proteins called SNAREs (soluble NSF attachment protein (SNAP) receptors). SNARE proteins are believed to mediate most, if not all, cellular membrane fusion events. Most SNAREs are C-terminally anchored integral membrane proteins capable of entering into a coiled-coil interaction with other SNARE proteins. All SNARE proteins share a homologous domain of approximately 60 amino acids referred to as the SNARE domain. The SNARE domain acts as a protein-protein interaction module in the assembly of a SNARE protein complex. While monomeric SNARE motifs are largely unstructured, they assemble into a protease resistant core complex. Interestingly, different SNARE family members are distributed on distinct membranes throughout the cell, suggesting the may play a role in targeting during vesicular transport. However, the formation of SNARE core complexes appears to be rather promiscuous with little specificity.
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Examples of Proteins:
| SNARE complex |
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SNARE domain proteins in complex |
| Rat synaptic fusion SNARE complex |  |
type1 TGF-b receptor BMPR-I group of receptors ALK1 group of receptors |
| Yeast exocytic post-Golgi SNARE complex | |
Snc2, Sso1, Sec9 |
| Rat endosomal SNARE complex | |
Syntaxin 7, Vti 1b, Syntaxin 8 |
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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