Taxonomic distribution of proteins containing t_SNARE domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing t_SNARE domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Evidence of domain swapping within the jumonji family of transcription factors.

Balciunas D, Ronne H
Trends Biochem Sci. 2000; 25: 274-6

Rapid and efficient fusion of phospholipid vesicles by the alpha-helical core of a SNARE complex in the absence of an N-terminal regulatory domain.

Parlati F, Weber T, McNew JA, Westermann B, Sollner TH, Rothman JE
Proc Natl Acad Sci U S A. 1999; 96: 12565-70

A protease-resistant core domain of the neuronal SNARE complex consists of an alpha-helical bundle similar to the proposed fusogenic core of viral fusion proteins [Skehel, J. J. & Wiley, D. C. (1998) Cell 95, 871-874]. We find that the isolated core of a SNARE complex efficiently fuses artificial bilayers and does so faster than full length SNAREs. Unexpectedly, a dramatic increase in speed results from removal of the N-terminal domain of the t-SNARE syntaxin, which does not affect the rate of assembly of v-t SNARES. In the absence of this negative regulatory domain, the half-time for fusion of an entire population of lipid vesicles by isolated SNARE cores ( approximately 10 min) is compatible with the kinetics of fusion in many cell types.

Membrane fusion: all done with SNAREpins?

Edwardson JM
Curr Biol. 1998; 8: 3903-3903

SNARE proteins are sufficient to fuse artificial membranes together. In the cell, vesicle transport may rely on fusion mediated by interaction between vesicle (v) and target (t) SNAREs, whereas the homotypic fusion of organelle biogenesis may be mediated by t-SNARE-t-SNARE interaction.

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

Fasshauer D, Sutton RB, Brunger AT, Jahn R
Proc Natl Acad Sci U S A. 1998; 95: 15781-6

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.

Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A.

Fernandez I, Ubach J, Dulubova I, Zhang X, Sudhof TC, Rizo J
Cell. 1998; 94: 841-9

Syntaxin 1A plays a central role in neurotransmitter release through multiple protein-protein interactions. We have used NMR spectroscopy to identify an autonomously folded N-terminal domain in syntaxin 1A and to elucidate its three-dimensional structure. This 120-residue N-terminal domain is conserved in plasma membrane syntaxins but not in other syntaxins, indicating a specific role in exocytosis. The domain contains three long alpha helices that form an up-and-down bundle with a left-handed twist. A striking residue conservation is observed throughout a long groove that is likely to provide a specific surface for protein-protein interactions. A highly acidic region binds to the C2A domain of synaptotagmin I in a Ca2+-dependent interaction that may serve as an electrostatic switch in neurotransmitter release.

Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p.

Nicholson KL, Munson M, Miller RB, Filip TJ, Fairman R, Hughson FM
Nat Struct Biol. 1998; 5: 793-802

The fusion of intracellular transport vesicles with their target membranes requires the assembly of SNARE proteins anchored in the apposed membranes. Here we use recombinant cytoplasmic domains of the yeast SNAREs involved in Golgi to plasma membrane trafficking to examine this assembly process in vitro. Binary complexes form between the target membrane SNAREs Sso1p and Sec9p; these binary complexes can subsequently bind to the vesicle SNARE Snc2p to form ternary complexes. Binary and ternary complex assembly are accompanied by large increases in alpha-helical structure, indicating that folding and complex formation are linked. Surprisingly, we find that binary complex formation is extremely slow, with a second-order rate constant of approximately 3 M(-1) s(-1). An N-terminal regulatory domain of Sso1p accounts for slow assembly, since in its absence complexes assemble 2,000-fold more rapidly. Once binary complexes form, ternary complex formation is rapid and is not affected by the presence of the regulatory domain. Our results imply that proteins that accelerate SNARE assembly in vivo act by relieving inhibition by this regulatory domain.

The synaptic SNARE complex is a parallel four-stranded helical bundle.

Poirier MA, Xiao W, Macosko JC, Chan C, Shin YK, Bennett MK
Nat Struct Biol. 1998; 5: 765-9

The heterotrimeric synaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of the synaptic vesicle-associated membrane protein 2 (VAMP2) and presynaptic plasma membrane proteins SNAP-25 (synaptosome-associated protein of 25,000 Mr) and syntaxin 1A, is a critical component of the exocytotic machinery. We have used spin labeling electron paramagnetic resonance spectroscopy to investigate the structural organization of this complex, particularly the two predicted helical domains contributed by SNAP-25. Our results indicate that the N- and C-terminal domains of SNAP-25 are parallel to each other and to the C-terminal domain of syntaxin 1A. Based on these findings, we propose a parallel four-stranded coiled coil model for the structure of the synaptic SNARE complex.

Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution.

Sutton RB, Fasshauer D, Jahn R, Brunger AT
Nature. 1998; 395: 347-53

The evolutionarily conserved SNARE proteins and their complexes are involved in the fusion of vesicles with their target membranes; however, the overall organization and structural details of these complexes are unknown. Here we report the X-ray crystal structure at 2.4 A resolution of a core synaptic fusion complex containing syntaxin-1 A, synaptobrevin-II and SNAP-25B. The structure reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion proteins. Conserved leucine-zipper-like layers are found at the centre of the synaptic fusion complex. Embedded within these leucine-zipper layers is an ionic layer consisting of an arginine and three glutamine residues contributed from each of the four alpha-helices. These residues are highly conserved across the entire SNARE family. The regions flanking the leucine-zipper-like layers contain a hydrophobic core similar to that of more general four-helix-bundle proteins. The surface of the synaptic fusion complex is highly grooved and possesses distinct hydrophilic, hydrophobic and charged regions. These characteristics may be important for membrane fusion and for the binding of regulatory factors affecting neurotransmission.

A model for structural similarity between different SNARE complexes based on sequence relationships.

Weimbs T, Mostov K, Low SH, Hofmann K
Trends Cell Biol. 1998; 8: 260-2

Structure determination of yeast cofilin.

Fedorov AA, Lappalainen P, Fedorov EV, Drubin DG, Almo SC
Nat Struct Biol. 1997; 4: 366-9

Cofilin, a ubiquitous 15,000 M(r) protein, plays a central role in regulating cytoskeletal dynamics. Cofilin binds to actin monomers and filaments, and has a pH-dependent actin severing activity. The structure will allow for a detailed analysis of cofilin function.

A conserved domain is present in different families of vesicular fusion proteins: a new superfamily.

Weimbs T, Low SH, Chapin SJ, Mostov KE, Bucher P, Hofmann K
Proc Natl Acad Sci U S A. 1997; 94: 3046-51

We have analyzed conserved domains in t-SNAREs [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors in the target membrane], proteins that are believed to be involved in the fusion of transport vesicles with their target membrane. By using a sensitive computer method, the generalized profile method, we were able to identify a new homology domain that is common in the two protein families previously identified to act as t-SNAREs, the syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) families, which therefore constitute a new superfamily. This homology domain of approximately 60 amino acids is predicted to form a coiled-coil structure. The significance of this homology domain could be demonstrated by a partial suppression of the coiled-coil properties of the domain profile. In proteins belonging to the syntaxin family, a single homology domain is located near the transmembrane domain, whereas the members of the SNAP-25 family possess two homology domains. This domain was also identified in several proteins that have been implicated in vesicular transport but do not belong to any of the t-SNARE protein families. Several new yeast, nematode, and mammalian proteins were identified that belong to the new superfamily. The evolutionary conservation of the SNARE coiled-coil homology domain suggests that this domain has a similar function in different membrane fusion proteins.