1. Structure of the Atg101–Atg13 complex reveals essential roles of Atg101 in autophagy initiation
- Author
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Takeshi Kaizuka, Noboru Mizushima, Nobuo N. Noda, and Hironori Suzuki
- Subjects
Models, Molecular ,Binding Sites ,Atg1 ,Mad2 ,Protein Conformation ,Chemistry ,Autophagy ,Autophagy-Related Proteins ,Autophagy-related protein 13 ,Crystallography, X-Ray ,Yeast ,Transport protein ,Cell biology ,Protein structure ,Structural Biology ,Schizosaccharomyces ,Protein Interaction Maps ,Schizosaccharomyces pombe Proteins ,Binding site ,Molecular Biology - Abstract
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.
- Published
- 2015
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