Journal Article

Structure of the Atg101–Atg13 complex reveals essential roles of Atg101 in autophagy initiation

Suzuki, Hironori, Kaizuka, Takeshi, Mizushima, Noboru, Noda, Nobuo N

2015

Overview

The crystal structure of the Atg101–Atg13 complex elucidates the function of Atg101 and sheds light on the molecular mechanisms of autophagy initiation in higher eukaryotes. Atg101 is an essential component of the autophagy-initiating ULK complex in higher eukaryotes, but it is absent from the functionally equivalent Atg1 complex in budding yeast. Here, we report the crystal structure of the fission yeast Atg101–Atg13 complex. Atg101 has a Hop1, Rev7 and Mad2 (HORMA) architecture similar to that of Atg13. Mad2 HORMA has two distinct conformations (O-Mad2 and C-Mad2), and, intriguingly, Atg101 resembles O-Mad2 rather than the C-Mad2–like Atg13. Atg13 HORMA from higher eukaryotes possesses an inherently unstable fold, which is stabilized by Atg101 via interactions analogous to those between O-Mad2 and C-Mad2. Mutational studies revealed that Atg101 is responsible for recruiting downstream factors to the autophagosome-formation site in mammals via a newly identified WF finger. These data define the molecular functions of Atg101, providing a basis for elucidating the molecular mechanisms of mammalian autophagy initiation by the ULK complex.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 13/1 / 13/31 / 14 / 631/535/1266 / 631/80/39 / Autophagy / Autophagy-Related Proteins / Binding Sites / Biochemistry / Biological Microscopy / Crystal structure / Crystallography, X-Ray / Life Sciences / Mammals / Membrane Biology / Models, Molecular / Molecular biology / Protein Conformation / Protein Interaction Maps / Protein Structure / Proteins / Schizosaccharomyces - chemistry / Schizosaccharomyces - cytology / Schizosaccharomyces - metabolism / Schizosaccharomyces pombe Proteins - chemistry / Schizosaccharomyces pombe Proteins - metabolism / Yeasts