|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of Human Atg12~Atg5 Conjugate in Complex with an N-terminal Fragment of Atg16L1== | | ==Crystal Structure of Human Atg12~Atg5 Conjugate in Complex with an N-terminal Fragment of Atg16L1== |
| - | <StructureSection load='4gdk' size='340' side='right' caption='[[4gdk]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4gdk' size='340' side='right'caption='[[4gdk]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gdk]] is a 6 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=4GDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GDK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gdk]] is a 6 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=4GDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GDK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gdl|4gdl]]</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=4gdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gdk OCA], [https://pdbe.org/4gdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gdk RCSB], [https://www.ebi.ac.uk/pdbsum/4gdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gdk ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APG12, APG12L, ATG12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APG5L, ASP, ATG5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), APG16L, ATG16L1, UNQ9393/PRO34307 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4gdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gdk OCA], [http://pdbe.org/4gdk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gdk RCSB], [http://www.ebi.ac.uk/pdbsum/4gdk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gdk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/A16L1_HUMAN A16L1_HUMAN]] Crohn disease. Disease susceptibility is associated with variations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ATG12_HUMAN ATG12_HUMAN]] Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through an ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus.<ref>PMID:12207896</ref> <ref>PMID:17709747</ref> <ref>PMID:19074260</ref> <ref>PMID:17999726</ref> <ref>PMID:19164948</ref> <ref>PMID:19666601</ref> <ref>PMID:23202584</ref> [[http://www.uniprot.org/uniprot/A16L1_HUMAN A16L1_HUMAN]] Plays an essential role in autophagy: interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II.<ref>PMID:23376921</ref> [[http://www.uniprot.org/uniprot/ATG5_HUMAN ATG5_HUMAN]] Involved in autophagy vesicles formation. Conjugation with ATG12 through an ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus. HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures; as well as in normal adipocyte differentiation.<ref>PMID:7796880</ref> <ref>PMID:12207896</ref> <ref>PMID:15778222</ref> <ref>PMID:17709747</ref> <ref>PMID:20580051</ref> <ref>PMID:22170153</ref> May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.<ref>PMID:7796880</ref> <ref>PMID:12207896</ref> <ref>PMID:15778222</ref> <ref>PMID:17709747</ref> <ref>PMID:20580051</ref> <ref>PMID:22170153</ref> | + | [https://www.uniprot.org/uniprot/ATG12_HUMAN ATG12_HUMAN] Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through an ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus.<ref>PMID:12207896</ref> <ref>PMID:17709747</ref> <ref>PMID:19074260</ref> <ref>PMID:17999726</ref> <ref>PMID:19164948</ref> <ref>PMID:19666601</ref> <ref>PMID:23202584</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 4gdk" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4gdk" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Autophagy-related protein 3D structures|Autophagy-related protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Metlagel, Z]] | + | [[Category: Large Structures]] |
| - | [[Category: Otomo, C]] | + | [[Category: Metlagel Z]] |
| - | [[Category: Otomo, T]] | + | [[Category: Otomo C]] |
| - | [[Category: Takaesu, G]] | + | [[Category: Otomo T]] |
| - | [[Category: Autophagy]]
| + | [[Category: Takaesu G]] |
| - | [[Category: Cytoplasm and autophagosomal membrane]]
| + | |
| - | [[Category: E3 ligase]]
| + | |
| - | [[Category: Isopeptide bond]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein-protein complex]]
| + | |
| - | [[Category: Protein-protein conjugate]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Ubiquitin-like fold]]
| + | |
| - | [[Category: Ubiquitin-like protein]]
| + | |
| Structural highlights
Function
ATG12_HUMAN Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through an ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The autophagy factor ATG12~ATG5 conjugate exhibits E3 ligase-like activity which facilitates the lipidation of members of the LC3 family. The crystal structure of the human ATG12~ATG5 conjugate bound to the N-terminal region of ATG16L1, the factor that recruits the conjugate to autophagosomal membranes, reveals an integrated architecture in which ATG12 docks onto ATG5 through conserved residues. ATG12 and ATG5 are oriented such that other conserved residues on each molecule, including the conjugation junction, form a continuous surface patch. Mutagenesis data support the importance of both the interface between ATG12 and ATG5 and the continuous patch for E3 activity. The ATG12~ATG5 conjugate interacts with the E2 enzyme ATG3 with high affinity through another surface location that is exclusive to ATG12, suggesting a different role of the continuous patch in E3 activity. These findings provide a foundation for understanding the mechanism of LC3 lipidation.
Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy.,Otomo C, Metlagel Z, Takaesu G, Otomo T Nat Struct Mol Biol. 2012 Dec 2. doi: 10.1038/nsmb.2431. PMID:23202584[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E. Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1164-70. PMID:12207896
- ↑ Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5. Epub 2007 Aug 20. PMID:17709747 doi:http://dx.doi.org/10.1073/pnas.0704014104
- ↑ Kim PK, Hailey DW, Mullen RT, Lippincott-Schwartz J. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20567-74. doi:, 10.1073/pnas.0810611105. Epub 2008 Dec 12. PMID:19074260 doi:http://dx.doi.org/10.1073/pnas.0810611105
- ↑ Fader CM, Sanchez D, Furlan M, Colombo MI. Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic. 2008 Feb;9(2):230-50. Epub 2007 Dec 7. PMID:17999726 doi:http://dx.doi.org/10.1111/j.1600-0854.2007.00677.x
- ↑ Terebiznik MR, Raju D, Vazquez CL, Torbricki K, Kulkarni R, Blanke SR, Yoshimori T, Colombo MI, Jones NL. Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells. Autophagy. 2009 Apr;5(3):370-9. Epub 2009 Apr 19. PMID:19164948
- ↑ Dreux M, Gastaminza P, Wieland SF, Chisari FV. The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14046-51. doi:, 10.1073/pnas.0907344106. Epub 2009 Aug 3. PMID:19666601 doi:http://dx.doi.org/10.1073/pnas.0907344106
- ↑ Otomo C, Metlagel Z, Takaesu G, Otomo T. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Mol Biol. 2012 Dec 2. doi: 10.1038/nsmb.2431. PMID:23202584 doi:http://dx.doi.org/10.1038/nsmb.2431
- ↑ Otomo C, Metlagel Z, Takaesu G, Otomo T. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat Struct Mol Biol. 2012 Dec 2. doi: 10.1038/nsmb.2431. PMID:23202584 doi:http://dx.doi.org/10.1038/nsmb.2431
|
