4wy4: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<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>
<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='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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</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>
</table>
</table>
== Function ==
== Function ==
[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>  
[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>  
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== 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<ref>PMID:25686604</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4wy4" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==

Latest revision as of 12:59, 1 March 2024

Crystal structure of autophagic SNARE complex

4wy4, resolution 1.40Å

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