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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Autophagy / physiology*
  • Autophagy-Related Proteins
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Analysis, Protein
  • Serine / chemistry
  • Serine / metabolism

Substances

  • ATG13 protein, S cerevisiae
  • Adaptor Proteins, Signal Transducing
  • Atg17 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Saccharomyces cerevisiae Proteins
  • Serine
  • Protein Kinases
  • ATG1 protein, S cerevisiae

Associated data

  • PDB/4P1N
  • PDB/4P1W