7JHX

Crystal structure of hEPG5 LIR/GABARAPL1 complex

7JHX の概要

• エントリーDOI: 10.2210/pdb7jhx/pdb
• 分子名称: Gamma-aminobutyric acid receptor-associated protein-like 1, Ectopic P granules protein 5 homolog, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: complex, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 32110.24

構造登録者

Cheung, Y.W.S.,Yip, C.K. (登録日: 2020-07-21, 公開日: 2021-03-17, 最終更新日: 2023-10-18)

主引用文献

Nam, S.E.,Cheung, Y.W.S.,Nguyen, T.N.,Gong, M.,Chan, S.,Lazarou, M.,Yip, C.K.
Insights on autophagosome-lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5.
Commun Biol, 4:291-291, 2021

PubMed Abstract: Pivotal to the maintenance of cellular homeostasis, macroautophagy (hereafter autophagy) is an evolutionarily conserved degradation system that involves sequestration of cytoplasmic material into the double-membrane autophagosome and targeting of this transport vesicle to the lysosome/late endosome for degradation. EPG5 is a large-sized metazoan protein proposed to serve as a tethering factor to enforce autophagosome-lysosome/late endosome fusion specificity, and its deficiency causes a severe multisystem disorder known as Vici syndrome. Here, we show that human EPG5 (hEPG5) adopts an extended "shepherd's staff" architecture. We find that hEPG5 binds preferentially to members of the GABARAP subfamily of human ATG8 proteins critical to autophagosome-lysosome fusion. The hEPG5-GABARAPs interaction, which is mediated by tandem LIR motifs that exhibit differential affinities, is required for hEPG5 recruitment to mitochondria during PINK1/Parkin-dependent mitophagy. Lastly, we find that the Vici syndrome mutation Gln336Arg does not affect the hEPG5's overall stability nor its ability to engage in interaction with the GABARAPs. Collectively, results from our studies reveal new insights into how hEPG5 recognizes mature autophagosome and establish a platform for examining the molecular effects of Vici syndrome disease mutations on hEPG5.

PubMed: 33674710
DOI: 10.1038/s42003-021-01830-x

実験手法

X-RAY DIFFRACTION (1.91 Å)