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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.<ref name="sutton" /><ref name="anto" /> 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.<ref> PMID: 12496247 </ref> 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.  
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.<ref name="sutton" /><ref name="anto" /> 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, <scene name='56/568021/Asp_156/2'>D156</scene> 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.<ref> PMID: 12496247 </ref> 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.  


Regarding the SNARE motifs, they are not only connected by the central interacting layers, but also '''by surface interactions''' that often involve side chains with complementary charges. As an example, an interaction between the helices of '''syntaxin 6''' and '''vti1a''' involves a '''hydrogen bond''' between '''E143 (vti1a)''' and '''S179 (sx6)'''. At a similar position in the late endosomal complex, a '''salt bridge''' is observed between '''D157 (vti1b)''' and '''R164 (sx8)'''.<ref name="anto" /> It has to be noted that all these side chains are '''highly conserved''' between the respective SNAREs of ''Drosophila'' and mammals. Many other surface interactions connect the SNARE motifs. However, the role of these surface interactions in the stability of the whole complex is still unknown.  
Regarding the SNARE motifs, they are not only connected by the central interacting layers, but also '''by surface interactions''' that often involve side chains with complementary charges. As an example, an interaction between the helices of '''syntaxin 6''' and '''vti1a''' involves a '''hydrogen bond''' between '''E143 (vti1a)''' and '''S179 (sx6)'''. At a similar position in the late endosomal complex, a '''salt bridge''' is observed between '''D157 (vti1b)''' and '''R164 (sx8)'''.<ref name="anto" /> It has to be noted that all these side chains are '''highly conserved''' between the respective SNAREs of ''Drosophila'' and mammals. Many other surface interactions connect the SNARE motifs. However, the role of these surface interactions in the stability of the whole complex is still unknown.  

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA, Camille Roesch, Hamelin Baptiste