title: Structure of the Atg101-Atg13 complex reveals essential roles of Atg101 in autophagy initiation.
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.
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaizuka
authors.affiliation: Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
authors.affiliation: 1] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2] Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Noda
mesh_terms: D001343:Autophagy; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D060066:Protein Interaction Maps; D012568:Schizosaccharomyces / Q000737:chemistry* / Q000166:cytology* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C000601557:Atg101 protein, S pombe; C000601558:Atg13 protein, S pombe; D000071183:Autophagy-Related Proteins; D029702:Schizosaccharomyces pombe Proteins