View source for 4naw


==Crystal Structure of Human ATG12~ATG5-ATG16N in complex with a fragment of ATG3==
<StructureSection load='4naw' size='340' side='right'caption='[[4naw]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4naw]] is a 16 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=4NAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NAW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.195&#8491;</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4naw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4naw OCA], [https://pdbe.org/4naw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4naw RCSB], [https://www.ebi.ac.uk/pdbsum/4naw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4naw ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
The autophagic ubiquitin-like protein (ublp) autophagy-related (ATG)12 is a component of the ATG12 approximately ATG5-ATG16L1 E3 complex that promotes lipid conjugation of members of the LC3 ublp family. A role of ATG12 in the E3 complex is to recruit the E2 enzyme ATG3. Here we report the identification of the ATG12 binding sequence in the flexible region of human ATG3 and the crystal structure of the minimal E3 complexed with the identified binding fragment of ATG3. The structure shows that 13 residues of the ATG3 fragment form a short beta-strand followed by an alpha-helix on a surface area that is exclusive to ATG12. Mutational analyses of ATG3 confirm that four residues whose side chains make contacts with ATG12 are important for E3 interaction as well as LC3 lipidation. Conservation of these four critical residues is high in metazoan organisms and plants but lower in fungi. A structural comparison reveals that the ATG3 binding surface on ATG12 contains a hydrophobic pocket corresponding to the binding pocket of LC3 that accommodates the leucine of the LC3-interacting region motif. These findings establish the mechanism of ATG3 recruitment by ATG12 in higher eukaryotes and place ATG12 among the members of signaling ublps that bind liner sequences.

Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12.,Metlagel Z, Otomo C, Takaesu G, Otomo T Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18844-9. doi:, 10.1073/pnas.1314755110. Epub 2013 Nov 4. PMID:24191030<ref>PMID:24191030</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4naw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Autophagy-related protein 3D structures|Autophagy-related protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Metlagel Z]]
[[Category: Otomo C]]
[[Category: Otomo T]]
[[Category: Takaesu G]]