5azf

From Proteopedia

(Difference between revisions)

Revision as of 08:50, 1 January 2020

Crystal structure of LGG-1 complexed with a WEEL peptide

Structural highlights

5azf is a 4 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5azg, 5azh
Gene:	lgg-1, C32D5.9 (CAEEL)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LGG1_CAEEL] Ubiquitin-like modifier involved in autophagy and essential for dauer development and life-span extension (PubMed:12958363, PubMed:20523114). Plays a role in mitophagy (PubMed:25896323).^[1] ^[2] ^[3] [ATG19_YEAST] Cargo-receptor protein involved in the cytoplasm to vacuole transport (Cvt) and in autophagy. Recognizes cargo proteins, such as APE4, LAP3, LAP4 and AMS1 and delivers them to the pre-autophagosomal structure for eventual engulfment by the autophagosome and targeting to the vacuole. Involved in the organization of the preautophagosomal structure (PAS). ATG19 association with cargo protein is required to localize ATG11 to the PAS. Also involved in endoplasmic reticulum-specific autophagic process, in selective removal of ER-associated degradation (ERAD) substrates, and is essential for the survival of cells subjected to severe ER stress. Plays also a role in regulation of filamentous growth.^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] ^[19]

Publication Abstract from PubMed

Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.

Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.,Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H Mol Cell. 2015 Dec 17;60(6):914-29. doi: 10.1016/j.molcel.2015.11.019. PMID:26687600^[20]

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

References

↑ Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003 Sep 5;301(5638):1387-91. PMID:12958363 doi:http://dx.doi.org/10.1126/science.1087782
↑ Alberti A, Michelet X, Djeddi A, Legouis R. The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. Autophagy. 2010 Jul;6(5):622-33. doi: 10.4161/auto.6.5.12252. Epub 2010 Jul 1. PMID:20523114 doi:http://dx.doi.org/10.4161/auto.6.5.12252
↑ Palikaras K, Lionaki E, Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature. 2015 May 28;521(7553):525-8. doi: 10.1038/nature14300. Epub 2015 Apr 20. PMID:25896323 doi:http://dx.doi.org/10.1038/nature14300
↑ Leber R, Silles E, Sandoval IV, Mazon MJ. Yol082p, a novel CVT protein involved in the selective targeting of aminopeptidase I to the yeast vacuole. J Biol Chem. 2001 Aug 3;276(31):29210-7. Epub 2001 May 29. PMID:11382752 doi:http://dx.doi.org/10.1074/jbc.M101438200
↑ Scott SV, Guan J, Hutchins MU, Kim J, Klionsky DJ. Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. Mol Cell. 2001 Jun;7(6):1131-41. PMID:11430817
↑ Suzuki K, Kamada Y, Ohsumi Y. Studies of cargo delivery to the vacuole mediated by autophagosomes in Saccharomyces cerevisiae. Dev Cell. 2002 Dec;3(6):815-24. PMID:12479807
↑ Shintani T, Huang WP, Stromhaug PE, Klionsky DJ. Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. Dev Cell. 2002 Dec;3(6):825-37. PMID:12479808
↑ Shintani T, Klionsky DJ. Cargo proteins facilitate the formation of transport vesicles in the cytoplasm to vacuole targeting pathway. J Biol Chem. 2004 Jul 16;279(29):29889-94. Epub 2004 May 11. PMID:15138258 doi:http://dx.doi.org/10.1074/jbc.M404399200
↑ Cebollero E, Carrascosa AV, Gonzalez R. Evidence for yeast autophagy during simulation of sparkling wine aging: a reappraisal of the mechanism of yeast autolysis in wine. Biotechnol Prog. 2005 Mar-Apr;21(2):614-6. PMID:15801807 doi:http://dx.doi.org/10.1021/bp049708y
↑ Baxter BK, Abeliovich H, Zhang X, Stirling AG, Burlingame AL, Goldfarb DS. Atg19p ubiquitination and the cytoplasm to vacuole trafficking pathway in yeast. J Biol Chem. 2005 Nov 25;280(47):39067-76. Epub 2005 Sep 26. PMID:16186126 doi:http://dx.doi.org/10.1074/jbc.M508064200
↑ Yorimitsu T, Klionsky DJ. Atg11 links cargo to the vesicle-forming machinery in the cytoplasm to vacuole targeting pathway. Mol Biol Cell. 2005 Apr;16(4):1593-605. Epub 2005 Jan 19. PMID:15659643 doi:http://dx.doi.org/10.1091/mbc.E04-11-1035
↑ Bernales S, McDonald KL, Walter P. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biol. 2006 Nov;4(12):e423. PMID:17132049 doi:http://dx.doi.org/10.1371/journal.pbio.0040423
↑ Ma J, Jin R, Dobry CJ, Lawson SK, Kumar A. Overexpression of autophagy-related genes inhibits yeast filamentous growth. Autophagy. 2007 Nov-Dec;3(6):604-9. Epub 2007 Jul 24. PMID:17700056
↑ Chang CY, Huang WP. Atg19 mediates a dual interaction cargo sorting mechanism in selective autophagy. Mol Biol Cell. 2007 Mar;18(3):919-29. Epub 2006 Dec 27. PMID:17192412 doi:http://dx.doi.org/10.1091/mbc.E06-08-0683
↑ Mazon MJ, Eraso P, Portillo F. Efficient degradation of misfolded mutant Pma1 by endoplasmic reticulum-associated degradation requires Atg19 and the Cvt/autophagy pathway. Mol Microbiol. 2007 Feb;63(4):1069-77. PMID:17238920 doi:http://dx.doi.org/10.1111/j.1365-2958.2006.05580.x
↑ Kageyama T, Suzuki K, Ohsumi Y. Lap3 is a selective target of autophagy in yeast, Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2009 Jan 16;378(3):551-7. doi:, 10.1016/j.bbrc.2008.11.084. Epub 2008 Dec 4. PMID:19061865 doi:http://dx.doi.org/10.1016/j.bbrc.2008.11.084
↑ Kario E, Amar N, Elazar Z, Navon A. A new autophagy-related checkpoint in the degradation of an ERAD-M target. J Biol Chem. 2011 Apr 1;286(13):11479-91. doi: 10.1074/jbc.M110.177618. Epub 2011, Jan 12. PMID:21228276 doi:http://dx.doi.org/10.1074/jbc.M110.177618
↑ Noda NN, Kumeta H, Nakatogawa H, Satoo K, Adachi W, Ishii J, Fujioka Y, Ohsumi Y, Inagaki F. Structural basis of target recognition by Atg8/LC3 during selective autophagy. Genes Cells. 2008 Oct 22. PMID:19021777 doi:GTC1238
↑ Watanabe Y, Noda NN, Kumeta H, Suzuki K, Ohsumi Y, Inagaki F. Selective transport of alpha-mannosidase by autophagic pathways: structural basis for cargo recognition by Atg19 and Atg34. J Biol Chem. 2010 Sep 24;285(39):30026-33. Epub 2010 Jul 21. PMID:20659891 doi:http://dx.doi.org/10.1074/jbc.M110.143545
↑ Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H. Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. Mol Cell. 2015 Dec 17;60(6):914-29. doi: 10.1016/j.molcel.2015.11.019. PMID:26687600 doi:http://dx.doi.org/10.1016/j.molcel.2015.11.019

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/5azf"

@@ Line 1: / Line 1: @@
 ==Crystal structure of LGG-1 complexed with a WEEL peptide==
-<StructureSection load='5azf' size='340' side='right' caption='[[5azf]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='5azf' size='340' side='right'caption='[[5azf]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5azf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AZF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5azf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AZF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5azg|5azg]], [[5azh|5azh]]</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=5azf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azf OCA], [http://pdbe.org/5azf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5azf RCSB], [http://www.ebi.ac.uk/pdbsum/5azf PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lgg-1, C32D5.9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</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=5azf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azf OCA], [http://pdbe.org/5azf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5azf RCSB], [http://www.ebi.ac.uk/pdbsum/5azf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5azf ProSAT]</span></td></tr>
 </table>
 == Function ==
 [[http://www.uniprot.org/uniprot/LGG1_CAEEL LGG1_CAEEL]] Ubiquitin-like modifier involved in autophagy and essential for dauer development and life-span extension (PubMed:12958363, PubMed:20523114). Plays a role in mitophagy (PubMed:25896323).<ref>PMID:12958363</ref> <ref>PMID:20523114</ref> <ref>PMID:25896323</ref>  [[http://www.uniprot.org/uniprot/ATG19_YEAST ATG19_YEAST]] Cargo-receptor protein involved in the cytoplasm to vacuole transport (Cvt) and in autophagy. Recognizes cargo proteins, such as APE4, LAP3, LAP4 and AMS1 and delivers them to the pre-autophagosomal structure for eventual engulfment by the autophagosome and targeting to the vacuole. Involved in the organization of the preautophagosomal structure (PAS). ATG19 association with cargo protein is required to localize ATG11 to the PAS. Also involved in endoplasmic reticulum-specific autophagic process, in selective removal of ER-associated degradation (ERAD) substrates, and is essential for the survival of cells subjected to severe ER stress. Plays also a role in regulation of filamentous growth.<ref>PMID:11382752</ref> <ref>PMID:11430817</ref> <ref>PMID:12479807</ref> <ref>PMID:12479808</ref> <ref>PMID:15138258</ref> <ref>PMID:15801807</ref> <ref>PMID:16186126</ref> <ref>PMID:15659643</ref> <ref>PMID:17132049</ref> <ref>PMID:17700056</ref> <ref>PMID:17192412</ref> <ref>PMID:17238920</ref> <ref>PMID:19061865</ref> <ref>PMID:21228276</ref> <ref>PMID:19021777</ref> <ref>PMID:20659891</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.
+Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.,Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H Mol Cell. 2015 Dec 17;60(6):914-29. doi: 10.1016/j.molcel.2015.11.019. PMID:26687600<ref>PMID:26687600</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5azf" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Caeel]]
+[[Category: Large Structures]]
 [[Category: Noda, N N]]
 [[Category: Watanabe, Y]]

5azf

From Proteopedia

Revision as of 08:50, 1 January 2020

Crystal structure of LGG-1 complexed with a WEEL peptide

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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