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Nat Struct Mol Biol. 2015 Jul;22(7):572-80. doi: 10.1038/nsmb.3036. Epub 2015 Jun 1.

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

Author information

1
Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
2
Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
3
1] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2] Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Tokyo, Japan.

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.

PMID:
26030876
DOI:
10.1038/nsmb.3036
[Indexed for MEDLINE]

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