TY  - INPR
A1  - Nishimura, Taki
A1  - Lazzeri, Gianmarco
A1  - Mizushima, Noboru
A1  - Covino, Roberto
A1  - Tooze, Sharon A.
T1  - Unique amphipathic α-helix drives membrane insertion and enzymatic activity of ATG3
T2  - bioRxiv
N2  - Autophagosome biogenesis requires a localized perturbation of lipid membrane dynamics and a unique protein-lipid conjugate. Autophagy-related (ATG) proteins catalyze this biogenesis on cellular membranes, but the underlying molecular mechanism remains unclear. Focusing on the final step of the protein-lipid conjugation reaction, ATG8/LC3 lipidation, we show how membrane association of the conjugation machinery is organized and fine-tuned at the atomistic level. Amphipathic α-helices in ATG3 proteins (AHATG3) are found to have low hydrophobicity and to be less bulky. Molecular dynamics simulations reveal that AHATG3 regulates the dynamics and accessibility of the thioester bond of the ATG3∼LC3 conjugate to lipids, allowing covalent lipidation of LC3. Live cell imaging shows that the transient membrane association of ATG3 with autophagic membranes is governed by the less bulky- hydrophobic feature of AHATG3. Collectively, the unique properties of AHATG3 facilitate protein- lipid bilayer association leading to the remodeling of the lipid bilayer required for the formation of autophagosomes.
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73171
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-731718
IS  - 2023.02.11.528101
ER  -