The carboxy terminus of yeast Atg13 binds phospholipid membrane via motifs that overlap with the Vac8-interacting domain |
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Authors: | Damián Gatica Alejandro Damasio Clarence Pascual |
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Institution: | 1. Department of Molecular, Cellular, and Developmental Biology, University of Michigan , Ann Arbor, MI, USA;2. Life Sciences Institute, University of Michigan , Ann Arbor, MI, USA;3. Department of Chemistry, Dartmouth College , Hanover, NH, USA;4. Life Sciences Institute, University of Michigan , Ann Arbor, MI, USA https://orcid.org/0000-0001-5746-0399 |
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Abstract: | 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. |
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Keywords: | Autophagy intrinsically disordered region membrane binding phospholipids structure |
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