8FKM

Human Atg3 with deletions of residues 1 to 25 and 90 to 190

Summary for 8FKM

• Entry DOI: 10.2210/pdb8fkm/pdb
• NMR Information: BMRB: 31065
• Descriptor: Ubiquitin-like-conjugating enzyme ATG3 (1 entity in total)
• Functional Keywords: conjugase, atg3, autophagy, ligase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 22091.42

Authors

Ye, Y.S.,Tian, F. (deposition date: 2022-12-21, release date: 2023-09-13, Last modification date: 2024-05-01)

Primary citation

Ye, Y.,Tyndall, E.R.,Bui, V.,Bewley, M.C.,Wang, G.,Hong, X.,Shen, Y.,Flanagan, J.M.,Wang, H.G.,Tian, F.
Multifaceted membrane interactions of human Atg3 promote LC3-phosphatidylethanolamine conjugation during autophagy.
Nat Commun, 14:5503-5503, 2023

PubMed Abstract: Autophagosome formation, a crucial step in macroautophagy (autophagy), requires the covalent conjugation of LC3 proteins to the amino headgroup of phosphatidylethanolamine (PE) lipids. Atg3, an E2-like enzyme, catalyzes the transfer of LC3 from LC3-Atg3 to PEs in targeted membranes. Here we show that the catalytically important C-terminal regions of human Atg3 (hAtg3) are conformationally dynamic and directly interact with the membrane, in collaboration with its N-terminal membrane curvature-sensitive helix. The functional relevance of these interactions was confirmed by in vitro conjugation and in vivo cellular assays. Therefore, highly curved phagophoric rims not only serve as a geometric cue for hAtg3 recruitment, but also their interaction with hAtg3 promotes LC3-PE conjugation by targeting its catalytic center to the membrane surface and bringing substrates into proximity. Our studies advance the notion that autophagosome biogenesis is directly guided by the spatial interactions of Atg3 with highly curved phagophoric rims.

PubMed: 37679347
DOI: 10.1038/s41467-023-41243-4

Experimental method

SOLUTION NMR