|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4wy4' size='340' side='right'caption='[[4wy4]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='4wy4' size='340' side='right'caption='[[4wy4]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wy4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WY4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wy4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WY4 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VAMP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), STX17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SNAP29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wy4 OCA], [https://pdbe.org/4wy4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wy4 RCSB], [https://www.ebi.ac.uk/pdbsum/4wy4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wy4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wy4 OCA], [http://pdbe.org/4wy4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wy4 RCSB], [http://www.ebi.ac.uk/pdbsum/4wy4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wy4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/SNP29_HUMAN SNP29_HUMAN]] CEDNIK syndrome. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SNP29_HUMAN SNP29_HUMAN]] SNAREs, Soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Probably involved in multiple membrane trafficking steps.<ref>PMID:23217709</ref> [[http://www.uniprot.org/uniprot/VAMP8_HUMAN VAMP8_HUMAN]] SNAREs, Soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also required for dense-granule secretion in platelets. Plays also a role in regulated enzyme secretion in pancreatic acinar cells. Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells. Involved in the homotypic fusion of early and late endosomes.<ref>PMID:12130530</ref> <ref>PMID:23217709</ref> [[http://www.uniprot.org/uniprot/STX17_HUMAN STX17_HUMAN]] SNAREs, Soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. STX17 is a SNARE of the autophagosome involved in autophagy through the direct control of autophagosome membrane fusion with the lysosome membrane. May also play a role in the early secretory pathway where it may maintain the architecture of the endoplasmic reticulum-Golgi intermediate compartment/ERGIC and Golgi and/or regulate transport between the endoplasmic reticulum, the ERGIC and the Golgi (PubMed:21545355).<ref>PMID:21545355</ref> <ref>PMID:23217709</ref> | + | [https://www.uniprot.org/uniprot/VAMP8_HUMAN VAMP8_HUMAN] SNAREs, Soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also required for dense-granule secretion in platelets. Plays also a role in regulated enzyme secretion in pancreatic acinar cells. Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells. Involved in the homotypic fusion of early and late endosomes.<ref>PMID:12130530</ref> <ref>PMID:23217709</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 20: |
| | ==See Also== | | ==See Also== |
| | *[[Synaptosomal-associated protein|Synaptosomal-associated protein]] | | *[[Synaptosomal-associated protein|Synaptosomal-associated protein]] |
| - | *[[Syntaxin|Syntaxin]] | + | *[[Syntaxin 3D structures|Syntaxin 3D structures]] |
| | *[[Vesicle-associated membrane protein|Vesicle-associated membrane protein]] | | *[[Vesicle-associated membrane protein|Vesicle-associated membrane protein]] |
| | == References == | | == References == |
| Line 29: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brunger, A T]] | + | [[Category: Brunger AT]] |
| - | [[Category: Zhao, M]] | + | [[Category: Zhao M]] |
| - | [[Category: Autophagy]]
| + | |
| - | [[Category: Fusion]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Snare]]
| + | |
| Structural highlights
Function
VAMP8_HUMAN SNAREs, Soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also required for dense-granule secretion in platelets. Plays also a role in regulated enzyme secretion in pancreatic acinar cells. Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells. Involved in the homotypic fusion of early and late endosomes.[1] [2]
Publication Abstract from PubMed
Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes.,Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz LM, Li J, Vivona S, Pfuetzner RA, Brunger AT, Zhong Q Nature. 2015 Feb 9. doi: 10.1038/nature14147. PMID:25686604[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Polgar J, Chung SH, Reed GL. Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion. Blood. 2002 Aug 1;100(3):1081-3. PMID:12130530
- ↑ Itakura E, Kishi-Itakura C, Mizushima N. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell. 2012 Dec 7;151(6):1256-69. doi: 10.1016/j.cell.2012.11.001. PMID:23217709 doi:http://dx.doi.org/10.1016/j.cell.2012.11.001
- ↑ Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz LM, Li J, Vivona S, Pfuetzner RA, Brunger AT, Zhong Q. ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature. 2015 Feb 9. doi: 10.1038/nature14147. PMID:25686604 doi:http://dx.doi.org/10.1038/nature14147
|
