Talk:Sandbox Reserved 823: Difference between revisions
No edit summary |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 13: | Line 13: | ||
== '''Membrane fusion mechanism''' == | == '''Membrane fusion mechanism''' == | ||
[[Image:Membrane_fusion.jpg|thumbnail||800 px||right| | [[Image:Membrane_fusion.jpg|thumbnail||800 px||right| '''Membrane fusion mechanism.''']] | ||
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> | ||
| Line 27: | Line 27: | ||
The SNARE domain is approximately '''60-70 residues''' long and is located immediately adjacent to a C-terminal transmembrane anchor. It contains a r'''epeating 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 name="anto" /><ref> PMID: 9731768 </ref><ref name="sutton" /> 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 SNARE domain is approximately '''60-70 residues''' long and is located immediately adjacent to a C-terminal transmembrane anchor. It contains a r'''epeating 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 name="anto" /><ref> PMID: 9731768 </ref><ref name="sutton" /> 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> | ||
=== '' “0”-layers'' === | === '' “0”-layers'' === | ||
[[Image:Layers.png|thumbnail||800 px||left| | [[Image:Layers.png|thumbnail||800 px||left| '''Topology of the 16 layers of the SNARE complex.''']] | ||
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. | 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. | ||
| Line 41: | Line 43: | ||
[[Image:Snare_complex.jpg|thumbnail|| | [[Image:Snare_complex.jpg|thumbnail||600 px||center| '''Crystal structure of the early endosomal SNARE complex.''' | ||
(A) Backbone overlay of the early endosomal SNARE complex (in color) and the neuronal SNARE complex (gray). | |||
(B) N- to C-terminal view of the 0 layer containing the unusual aspartate in vti1a. (Color, early endosomal SNARE complex; gray, neuronal SNARE complex.) | |||
(C) Residue E143 builds a salt bridge with the residue S179. The residue E143 is also sandwiched by residues V182 and V140, which strengthen polar interactions. In the late endosomal and in the neuronal SNARE complex, this glutamate is conserved and interacts with a conserved arginine that occupies the position equivalent to V182. | |||
(D) View of the 0 layer, including hydrogen bonds with surface residues and water molecules. | |||
]] | |||
| Line 51: | Line 58: | ||
== ''' SNAREs | == ''' SNAREs and pulmonary hypertension ''' == | ||
'''Pulmonary hypertension''' (PH) corresponds to an '''increase of blood pressure''' in the pulmonary artery, pulmonary vein, or pulmonary capillaries leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms. Pulmonary hypertension can be a '''severe disease''', characterized by a decreased exercise tolerance and heart failure. The origin of the disease seems to be a golgi-dysfunction. Indeed, dysfunction of golgi tethers, SNAPs and '''SNAREs''' apparently leads to pulmonary hypertension.<ref> PMID:17416597 </ref> | '''Pulmonary hypertension''' (PH) corresponds to an '''increase of blood pressure''' in the pulmonary artery, pulmonary vein, or pulmonary capillaries leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms. Pulmonary hypertension can be a '''severe disease''', characterized by a decreased exercise tolerance and heart failure. The origin of the disease seems to be a golgi-dysfunction. Indeed, dysfunction of golgi tethers, SNAPs and '''SNAREs''' apparently leads to pulmonary hypertension.<ref> PMID:17416597 </ref> | ||
| Line 57: | Line 64: | ||
== '''References''' == | == '''References''' == | ||