Metamorphic proteins at the basis of human autophagy initiation and lipid transfer

• DOI: 10.1016/j.molcel.2023.04.026
• Publication Date: 2023-05-19T14:48:16Z
• Authors: Anh Nguyen; Francesca Lugarini; Céline David; Pouya Hosnani; Çağla Alagöz; Annabelle Friedrich; David Schlütermann; Barbora Knotkova; Anoshi Patel; Iwan Parfentev; Henning Urlaub; Michael Meinecke; Björn Stork; Alex C. Faesen
• Keywords: Basis (linear algebra)

Autophagy is a conserved intracellular degradation pathway that generates de novo double-membrane autophagosomes to target wide range of material for lysosomal degradation. In multicellular organisms, autophagy initiation requires the timely assembly contact site between ER and nascent autophagosome. Here, we report in vitro reconstitution full-length seven-subunit human supercomplex built on core complex ATG13-101 ATG9. Assembly this rare ability ATG13 ATG101 switch distinct folds. The slow spontaneous metamorphic conversion rate limiting self-assembly supercomplex. interaction with ATG2-WIPI4 enhances tethering membrane vesicles accelerates lipid transfer ATG2 by both ATG9 ATG13-101. Our work uncovers molecular basis its mechanisms imposed metamorphosis regulate autophagosome biogenesis space time.