6ojj

From Proteopedia

(Difference between revisions)

Revision as of 05:56, 21 August 2019

Structure of ScAtg3 with truncations in N-terminal and flexible region (FR)

Structural highlights

6ojj is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ATG3_YEAST] E2 conjugating enzyme responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8. This step is required for the membrane association of ATG8. The formation of the ATG8-phosphatidylethanolamine conjugate is essential for autophagy and for the cytoplasm to vacuole transport (Cvt).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Autophagy depends on the E2 enzyme, Atg3, functioning in a conserved E1-E2-E3 trienzyme cascade that catalyzes lipidation of Atg8-family ubiquitin-like proteins (UBLs). Molecular mechanisms underlying Atg8 lipidation remain poorly understood despite association of Atg3, the E1 Atg7, and the composite E3 Atg12-Atg5-Atg16 with pathologies including cancers, infections and neurodegeneration. Here, studying yeast enzymes, we report that an Atg3 element we term E123IR (E1, E2, and E3-interacting region) is an allosteric switch. NMR, biochemical, crystallographic and genetic data collectively indicate that in the absence of the enzymatic cascade, the Atg3(E123IR) makes intramolecular interactions restraining Atg3's catalytic loop, while E1 and E3 enzymes directly remove this brace to conformationally activate Atg3 and elicit Atg8 lipidation in vitro and in vivo. We propose that Atg3's E123IR protects the E2~UBL thioester bond from wayward reactivity toward errant nucleophiles, while Atg8 lipidation cascade enzymes induce E2 active site remodeling through an unprecedented mechanism to drive autophagy.

A switch element in the autophagy E2 Atg3 mediates allosteric regulation across the lipidation cascade.,Zheng Y, Qiu Y, Grace CRR, Liu X, Klionsky DJ, Schulman BA Nat Commun. 2019 Aug 9;10(1):3600. doi: 10.1038/s41467-019-11435-y. PMID:31399562^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M. AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae. J Bacteriol. 1997 Feb;179(4):1068-76. PMID:9023185
↑ Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993 Oct 25;333(1-2):169-74. PMID:8224160
↑ Thumm M, Egner R, Koch B, Schlumpberger M, Straub M, Veenhuis M, Wolf DH. Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett. 1994 Aug 1;349(2):275-80. PMID:8050581
↑ Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, Ishihara N, Mizushima N, Tanida I, Kominami E, Ohsumi M, Noda T, Ohsumi Y. A ubiquitin-like system mediates protein lipidation. Nature. 2000 Nov 23;408(6811):488-92. PMID:11100732 doi:10.1038/35044114
↑ Kim J, Huang WP, Klionsky DJ. Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. J Cell Biol. 2001 Jan 8;152(1):51-64. PMID:11149920
↑ Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. J Biol Chem. 2004 Sep 24;279(39):40584-92. Epub 2004 Jul 23. PMID:15277523 doi:10.1074/jbc.M405860200
↑ Zheng Y, Qiu Y, Grace CRR, Liu X, Klionsky DJ, Schulman BA. A switch element in the autophagy E2 Atg3 mediates allosteric regulation across the lipidation cascade. Nat Commun. 2019 Aug 9;10(1):3600. doi: 10.1038/s41467-019-11435-y. PMID:31399562 doi:http://dx.doi.org/10.1038/s41467-019-11435-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ojj"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6ojj is ON HOLD  until Paper Publication
+==Structure of ScAtg3 with truncations in N-terminal and flexible region (FR)==
+<StructureSection load='6ojj' size='340' side='right'caption='[[6ojj]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6ojj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OJJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OJJ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=6ojj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ojj OCA], [http://pdbe.org/6ojj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ojj RCSB], [http://www.ebi.ac.uk/pdbsum/6ojj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ojj ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ATG3_YEAST ATG3_YEAST]] E2 conjugating enzyme responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8. This step is required for the membrane association of ATG8. The formation of the ATG8-phosphatidylethanolamine conjugate is essential for autophagy and for the cytoplasm to vacuole transport (Cvt).<ref>PMID:9023185</ref> <ref>PMID:8224160</ref> <ref>PMID:8050581</ref> <ref>PMID:11100732</ref> <ref>PMID:11149920</ref> <ref>PMID:15277523</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Autophagy depends on the E2 enzyme, Atg3, functioning in a conserved E1-E2-E3 trienzyme cascade that catalyzes lipidation of Atg8-family ubiquitin-like proteins (UBLs). Molecular mechanisms underlying Atg8 lipidation remain poorly understood despite association of Atg3, the E1 Atg7, and the composite E3 Atg12-Atg5-Atg16 with pathologies including cancers, infections and neurodegeneration. Here, studying yeast enzymes, we report that an Atg3 element we term E123IR (E1, E2, and E3-interacting region) is an allosteric switch. NMR, biochemical, crystallographic and genetic data collectively indicate that in the absence of the enzymatic cascade, the Atg3(E123IR) makes intramolecular interactions restraining Atg3's catalytic loop, while E1 and E3 enzymes directly remove this brace to conformationally activate Atg3 and elicit Atg8 lipidation in vitro and in vivo. We propose that Atg3's E123IR protects the E2~UBL thioester bond from wayward reactivity toward errant nucleophiles, while Atg8 lipidation cascade enzymes induce E2 active site remodeling through an unprecedented mechanism to drive autophagy.
-Authors:
+A switch element in the autophagy E2 Atg3 mediates allosteric regulation across the lipidation cascade.,Zheng Y, Qiu Y, Grace CRR, Liu X, Klionsky DJ, Schulman BA Nat Commun. 2019 Aug 9;10(1):3600. doi: 10.1038/s41467-019-11435-y. PMID:31399562<ref>PMID:31399562</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6ojj" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Qiu, Y]]
+[[Category: Schulman, B A]]
+[[Category: Zheng, Y]]
+[[Category: Autophagy]]
+[[Category: E2]]
+[[Category: Ligase]]

6ojj

From Proteopedia

Revision as of 05:56, 21 August 2019

Structure of ScAtg3 with truncations in N-terminal and flexible region (FR)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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