4gdl
From Proteopedia
Crystal Structure of Human Atg12~Atg5 Conjugate in Complex with an N-terminal Fragment of Atg16L1
Structural highlights
FunctionATG12_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 PubMedThe 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 AlsoReferences
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