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Nat Struct Mol Biol. 2014 Jun;21(6):513-21. doi: 10.1038/nsmb.2822. Epub 2014 May 4.

Structural basis of starvation-induced assembly of the autophagy initiation complex.

Author information

  • 11] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2].
  • 21] Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan. [2] Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. [3].
  • 31] Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan. [2].
  • 4Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan.
  • 5Graduate School of Medical Life Science and Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
  • 6Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
  • 71] Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan. [2] Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
  • 81] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2] Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.

Abstract

Assembly 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.

PMID:
24793651
[PubMed - indexed for MEDLINE]
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