Talk:Sandbox Reserved 823: Difference between revisions

Important biological processes, such as synaptic transmission and cellular trafficking in Eukaryotes require SNARE proteins that are thought to play a crucial role in membrane fusion. .<ref> PMID: 11340056 </ref><ref> PMID: 11252968 </ref><ref> PMID: 12600315 </ref><ref> PMID: 12154365 </ref> To connect membranes and allow their fusion, SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) proteins assemble into a core-complex of four parallel helices.<ref> PMID: 11786915 </ref><ref> PMID: 9731768 </ref><ref> PMID: 9759724 </ref> The SNARE complex assembly is mediated by a conserved SNARE motif consisting of 60-70 amino acids. <ref> PMID: 9096343 </ref> SNAREs can be divided into two categories: the v-(vesicle) SNAREs, which are found in the vesicle membrane and the t-(target) SNAREs, which are anchored in the target membrane.<ref> PMID: 8455717 </ref>

The best-studied SNAREs are the neuronal and the early endosomal SNARE complexes. The Neuronal SNARE complex mediates exocytosis of synaptic vesicles in the neurons and includes the vesicle protein synaptobrevin (also called VAMP), the membrane proteins SNAP-25 and syntaxin 1.<ref> PMID: 9759724 </ref> The early endosomal SNARE complex includes syntaxin6, syntaxin13, vti1a and VAMP4 and is responsible for homotypic fusion of early endosomes.<ref> PMID: 16469845 </ref> It has been shown that the crystal structure of the early endosomal SNARE complex resembles that of the neuronal and late endosomal complexes, but differs in surface side-chain interactions.  

The SNARE domain is approximately 60-70 residues long and is located immediately adjacent to a C-terminal transmembrane anchor. It contains a repeating heptad pattern of hydrophobic residues. Their orientation places them in an alpha-helical structure so that all the hydrophobic side chains are located on the same face of the helix.<ref> PMID: 11786915 </ref><ref> PMID: 9731768 </ref><ref> PMID: 9759724 </ref> SNARE domains allow the four SNAREs protein to assemble into parallel four-helix bundles. This parallel arrangement brings the transmembrane anchors and the membranes closer. <ref> PMID: 9267032 </ref>

The early endosomal SNARE complex forms a four-helix bundle with a left-handed superhelical twist. The position of the Qa-, Qb-, Qc-, and R-SNAREs is the same in the neuronal and late endosomal complexes (Sutton et al, 1998b; Antonin et al., 2002). As mentioned above, an unconventional layer of hydrophilic residues – the “0”-layer – constituted of three glutamines and one arginine, characterizes the center of all SNARE complexes. However, in vti1a an aspartate residue substitutes the glutamine. The aspartate occupies the same position as the glutamine in the neuronal and late endosomal complexes, and is involved in a similar organization of hydrogen bonds with the other layer of amino acids. Moreover, in vti1a, D156 of the ‘0' layer also interacts with N152 at the surface of the vti1a helix and with a water molecule. Also, sx6 Q197 interacts with the backbone of vti1a D156 and with sx6 E193 that in turn interacts with vti1a R157. Concerning Vti1a R157, it interacts with sx6 E196. This network of interactions resembles that observed in the neuronal complex (Ernst and Brunger, 2003b). The structure of the other layers is generally similar to that of the neuronal and late endosomal complexes. Indeed, slightly differences can be noted: in layer 6, the Qc-SNARE syntaxin 6 contains a valine, whereas the late endosomal Qc-SNARE syntaxin 8 contains a glutamate, which is involved in interactions with surface residues. Such interactions are absent in the early endosomal and the neuronal complexes.