4p1n | pdb_00004p1n
Crystal structure of Atg1-Atg13 complex
Structural highlights
FunctionATG1_KLUMD Serine/threonine protein kinase involved in the cytoplasm to vacuole transport (Cvt) and found to be essential in autophagy, where it is required for the formation of autophagosomes (By similarity). Involved in the clearance of protein aggregates which cannot be efficiently cleared by the proteasome (By similarity). Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (By similarity). Also involved in endoplasmic reticulum-specific autophagic process, in selective removal of ER-associated degradation (ERAD) substrates (By similarity). Plays a key role in ATG9 and ATG23 cycling through the pre-autophagosomal structure and is necessary to promote ATG18 binding to ATG9 through phosphorylation of ATG9. Catalyzes phosphorylation of ATG4, decreasing the interaction between ATG4 and ATG8 and impairing deconjugation of PE-conjugated forms of ATG8 (By similarity).[UniProtKB:P53104] Publication Abstract from PubMedAssembly of the preautophagosomal structure (PAS) is essential for autophagy initiation in yeast. Starvation-induced dephosphorylation of Atg13 is required for the formation of the Atg1-Atg13-Atg17-Atg29-Atg31 complex (Atg1 complex), a prerequisite for PAS assembly. However, molecular details underlying these events have not been established. Here we studied the interactions of yeast Atg13 with Atg1 and Atg17 by X-ray crystallography. Atg13 binds tandem microtubule interacting and transport domains in Atg1, using an elongated helix-loop-helix region. Atg13 also binds Atg17, using a short region, thereby bridging Atg1 and Atg17 and leading to Atg1-complex formation. Dephosphorylation of specific serines in Atg13 enhanced its interaction with not only Atg1 but also Atg17. These observations update the autophagy-initiation model as follows: upon starvation, dephosphorylated Atg13 binds both Atg1 and Atg17, and this promotes PAS assembly and autophagy progression. Structural basis of starvation-induced assembly of the autophagy initiation complex.,Fujioka Y, Suzuki SW, Yamamoto H, Kondo-Kakuta C, Kimura Y, Hirano H, Akada R, Inagaki F, Ohsumi Y, Noda NN Nat Struct Mol Biol. 2014 May 4. doi: 10.1038/nsmb.2822. PMID:24793651[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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