8AFI

GABARAP in complex with LIR motif of HsATG3

8AFI の概要

• エントリーDOI: 10.2210/pdb8afi/pdb
• 分子名称: Gamma-aminobutyric acid receptor-associated protein, Ubiquitin-like-conjugating enzyme ATG3, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: autophagy, lir, atg3, gabarap, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 131837.77

構造登録者

Farnung, J.,Benoit, R.M.,Corn, J.E.,Bode, J.W. (登録日: 2022-07-18, 公開日: 2023-05-10, 最終更新日: 2024-02-07)

主引用文献

Farnung, J.,Muhar, M.,Liang, J.R.,Tolmachova, K.A.,Benoit, R.M.,Corn, J.E.,Bode, J.W.
Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical LC3 Interacting Region Motif Crucial for the Enzymatic Activity of Human ATG3.
Acs Cent.Sci., 9:1025-1034, 2023

PubMed Abstract: Macroautophagy is one of two major degradation systems in eukaryotic cells. Regulation and control of autophagy are often achieved through the presence of short peptide sequences called LC3 interacting regions (LIR) in autophagy-involved proteins. Using a combination of new protein-derived activity-based probes prepared from recombinant LC3 proteins, along with protein modeling and X-ray crystallography of the ATG3-LIR peptide complex, we identified a noncanonical LIR motif in the human E2 enzyme responsible for LC3 lipidation, ATG3. The LIR motif is present in the flexible region of ATG3 and adopts an uncommon β-sheet structure binding to the backside of LC3. We show that the β-sheet conformation is crucial for its interaction with LC3 and used this insight to design synthetic macrocyclic peptide-binders to ATG3. CRISPR-enabled studies provide evidence that LIR is required for LC3 lipidation and ATG3∼LC3 thioester formation. Removal of LIR negatively impacts the rate of thioester transfer from ATG7 to ATG3.

PubMed: 37252361
DOI: 10.1021/acscentsci.3c00009

実験手法

X-RAY DIFFRACTION (2.66 Å)