4naw: Difference between revisions
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{{STRUCTURE_4naw| PDB=4naw | SCENE= }} | |||
===Crystal Structure of Human ATG12~ATG5-ATG16N in complex with a fragment of ATG3=== | |||
==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== | |||
[[http://www.uniprot.org/uniprot/ATG3_HUMAN ATG3_HUMAN]] E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3.<ref>PMID:11825910</ref> <ref>PMID:12207896</ref> <ref>PMID:12890687</ref> <ref>PMID:16704426</ref> <ref>PMID:20723759</ref> [[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> | |||
==About this Structure== | |||
[[4naw]] is a 16 chain structure with sequence from [http://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]. | |||
==Reference== | |||
<references group="xtra"/><references/> | |||
[[Category: Homo sapiens]] | |||
[[Category: Metlagel, Z.]] | |||
[[Category: Otomo, C.]] | |||
[[Category: Otomo, T.]] | |||
[[Category: Takaesu, G.]] | |||
[[Category: Autophagy]] | |||
[[Category: E3 ligase]] | |||
[[Category: Protein transport-ligase complex]] | |||
[[Category: Protein-protein conjugate]] | |||
[[Category: Ubiquitin-like protein]] | |||
