Structure Synaptobrevin

Fig. 1 Structure of the neuronal SNAREs. Upper panel domain structure of the three neuronal SNARE proteins involved in synaptic vesicle fusion. Syntaxin 1A and SNAP-25 (contains two SNARE motifs) are associated with the presynaptic membrane, whereas synaptobrevin 2 is synaptic vesicle associated. The SNARE motifs form a stable complex (core complex) whose crystal structure has been analyzed (lower panel). In the complex, each of the SNARE motifs adopts an alpha-helical structure, and the four alpha-helices are aligned in parallel forming a twisted bundle (modified from Sutton et al. 1998). Stability of the complex is mediated by layers of interaction (—7 to +8) in which amino acids from each of the four alpha-helices participate (see text).

In addition to the proteins discussed above, neuronal SNAREs were reported to interact with numerous other proteins in a specific manner, but in most cases both the structural basis and the biological function of these interactions need to be defined. For instance, synaptophysin, a membrane protein of synaptic vesicles, forms a complex with synaptobrevin in which synaptobrevin is not available for interactions with its partner SNAREs syntaxin 1A and SNAP-25, suggesting that this complex represents a reserve pool of recruitable synaptobrevin (Becher et al. 1999) or regulates interactions between the vesicle-associated synaptobrevin and the plasmalem-mal SNAREs. Alternatively, it has been suggested that this complex is involved in synaptobrevin sorting to synaptic vesicles. 

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SNARE proteins assemble into a heterotrimeric SNARE complex (or core complex). The crystal structure of the core complex revealed a bundle of four a-helices, one each contributed by synaptobrevin and syntaxin and two contributed by SNAP-25 (28). The process of SNARE complex assembly proceeds from N-terminal to C-terminal direction in what is commonly referred to as a zippering action, which brings the C-terminal membrane anchors of the transSNAREs together (29). This action is proposed to force the closely apposed membranes together to initiate fusion. 

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The structure and interfacial association of the full-length vesicle SNARE, synaptobrevin (I), were compared in 4 different lipid environments using NMR and ESR spectroscopy. In micelles, segments of the SNARE motif were helical and associated with the interface. However, the fraction of helix and interfacial association decreased as I was moved from micelle to bicelle to bilayer environments, indicating that the tendency toward interfacial association was sensitive to membrane curvature. In bilayers, the SNARE motif of I transiently associated with the lipid interface, and regions that were helical in micelles were in conformational and environmental exchange in bicelles and bilayers. ... 

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