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Autophagy. 2019 Aug 2:1-14. doi: 10.1080/15548627.2019.1648117. [Epub ahead of print]

The carboxy terminus of yeast Atg13 binds phospholipid membrane via motifs that overlap with the Vac8-interacting domain.

Author information

1
a Department of Molecular, Cellular, and Developmental Biology, University of Michigan , Ann Arbor , MI , USA.
2
b Life Sciences Institute, University of Michigan , Ann Arbor , MI , USA.
3
c Department of Chemistry, Dartmouth College , Hanover , NH , USA.

Abstract

Macroautophagy/autophagy is a conserved catabolic recycling pathway involving the sequestration of cytoplasmic components within double-membrane vesicles termed autophagosomes. The autophagy-related (Atg) protein Atg13 is a key member of the autophagy initiation complex. The Atg13 C terminus is an intrinsically disordered region (IDR) harboring a binding site for the vacuolar membrane protein Vac8. Recent reports suggest Atg13 acts as a hub to assemble the initiation complex, and also participates in membrane recognition. Here we show that the Atg13 C terminus directly binds to lipid membranes via electrostatic interactions between positively charged residues in Atg13 and negatively charged phospholipids as well as a hydrophobic insertion of a Phe residue. We identified 2 sets of residues in the Atg13 IDR that affect its phospholipid-binding properties; these residues overlap with the Vac8-binding domain of Atg13. Our data indicate that Atg13 binding to phospholipids and Vac8 is mutually exclusive, and both are required for efficient autophagy. Abbreviations: Atg: autophagy-related; CD: circular dichroism; Cvt: cytoplasm-to-vacuole targeting; IDR: intrinsically disordered region; ITC: isothermal calorimetry; MIM: MIT-interacting motif; MKO: multiple-knockout; PAS: phagophore assembly site; PC: phosphatidylcholine; PS: phosphatidylserine; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate.

KEYWORDS:

Autophagy; intrinsically disordered region; membrane binding; phospholipids; structure

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