Talk:Sandbox Reserved 823: Difference between revisions
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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 name="anto"> PMID: 11786915 </ref><ref> PMID: 9731768 </ref><ref name="sutton"> 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> | 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 name="anto"> PMID: 11786915 </ref><ref> PMID: 9731768 </ref><ref name="sutton"> 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 name="sutton" /> '''The early endosomal SNARE complex''' includes ''' | 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 name="sutton" /> '''The early endosomal SNARE complex''' includes '''syntaxin 6, syntaxin 13, 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. | ||
== '''Membrane fusion mechanism''' == | == '''Membrane fusion mechanism''' == | ||
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Membrane Fusion requires the '''assembly of the core complex'''. '''Free t-SNAREs''' that are organized in '''clusters''' first assemble into acceptor complexes thanks to '''SM''' (Sec1/Munc18-related) '''proteins'''. Acceptor complexes can then interact with the '''v-SNAREs''' through the N-terminal domain of the SNARE motif. This enables the formation of '''four-helical trans-complexes''', in which only the N-terminal portions of the SNARE motifs are bound. This binding evolves from a '''loose''' to a '''tight state''', thus leading to the formation of a '''fusion pore'''. During the fusion, the conformation relaxes to a '''cis-configuration'''. Cis-complexes dissociate thanks to '''proteins''' and '''cofactors (SNAPs)'''. T- and v-SNAREs can be separated and recycled.<ref> PMID: 16912714 </ref> | Membrane Fusion requires the '''assembly of the core complex'''. '''Free t-SNAREs''' that are organized in '''clusters''' first assemble into acceptor complexes thanks to '''SM''' (Sec1/Munc18-related) '''proteins'''. Acceptor complexes can then interact with the '''v-SNAREs''' through the N-terminal domain of the SNARE motif. This enables the formation of '''four-helical trans-complexes''', in which only the N-terminal portions of the SNARE motifs are bound. This binding evolves from a '''loose''' to a '''tight state''', thus leading to the formation of a '''fusion pore'''. During the fusion, the conformation relaxes to a '''cis-configuration'''. Cis-complexes dissociate thanks to '''proteins''' and '''cofactors (SNAPs)'''. T- and v-SNAREs can be separated and recycled.<ref> PMID: 16912714 </ref> | ||
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=== '' “0”-layers'' === | === '' “0”-layers'' === | ||
The centre of the four-helix bundle is constituted of 16 layers. These layers are composed of hydrophobic side chains, which are perpendicular to the axis of the four-helix bundle, except for the central “0”-layer. This last one consists of three glutamine (Q) and one arginine (R) highly conserved residues | The centre of the four-helix bundle is constituted of '''16 layers'''. These layers are composed of '''hydrophobic side chains''', which are perpendicular to the axis of the four-helix bundle, except for the central '''“0”-layer'''. This last one consists of '''three glutamine (Q)''' and '''one arginine (R)''' highly conserved residues. Those highly conserved residues have led to a new classification of SNAREs into '''Q- and R-SNAREs'''. <ref> PMID: 9861047 </ref> Almost all membrane fusion reactions require one R-SNARE and three Q-SNAREs:Qa, Qb and Qc.<ref> PMID: 11237004 </ref><ref> PMID: 11001046 </ref> In many cases, the R-SNARE is in the vesicle, and the three Q-SNAREs are in the target membrane. For the early endosomal SNARE complex, syntaxin 13, vti1a, syntaxin 6, and VAMP4 were respectively classified as Qa-, Qb-, Qc- and R-SNAREs. | ||
=== ''Structure of the early endosomal SNARE complex 2NPS'' === | === ''Structure of the early endosomal SNARE complex 2NPS'' === | ||