7BV4

Crystal structure of STX17 LIR region in complex with GABARAP

7BV4 の概要

• エントリーDOI: 10.2210/pdb7bv4/pdb
• 分子名称: Gamma-aminobutyric acid receptor-associated protein, Syntaxin-17, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: autophagy, synatxin 17, 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: 8
• 化学式量合計: 65862.94

構造登録者

Li, Y.,Pan, L.F. (登録日: 2020-04-09, 公開日: 2020-09-02, 最終更新日: 2023-11-29)

主引用文献

Li, Y.,Cheng, X.,Li, M.,Wang, Y.,Fu, T.,Zhou, Z.,Wang, Y.,Gong, X.,Xu, X.,Liu, J.,Pan, L.
Decoding three distinct states of the Syntaxin17 SNARE motif in mediating autophagosome-lysosome fusion.
Proc.Natl.Acad.Sci.USA, 117:21391-21402, 2020

PubMed Abstract: Syntaxin17, a key autophagosomal -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, can associate with ATG8 family proteins SNAP29 and VAMP8 to facilitate the membrane fusion process between the double-membraned autophagosome and single-membraned lysosome in mammalian macroautophagy. However, the inherent properties of Syntaxin17 and the mechanistic basis underlying the interactions of Syntaxin17 with its binding proteins remain largely unknown. Here, using biochemical, NMR, and structural approaches, we systemically characterized Syntaxin17 as well as its interactions with ATG8 family proteins, SNAP29 and VAMP8. We discovered that Syntaxin17 alone adopts an autoinhibited conformation mediated by a direct interaction between its Habc domain and the Qa-SNARE motif. In addition, we revealed that the Qa-SNARE region of Syntaxin17 contains one LC3-interacting region (LIR) motif, which preferentially binds to GABARAP subfamily members. Importantly, the GABARAP binding of Syntaxin17 can release its autoinhibited state. The determined crystal structure of the Syntaxin17 LIR-GABARAP complex not only provides mechanistic insights into the interaction between Syntaxin17 and GABARAP but also reveals an unconventional LIR motif with a C-terminally extended 3 helix for selectively binding to ATG8 family proteins. Finally, we also elucidated structural arrangements of the autophagic Syntaxin17-SNAP29-VAMP8 SNARE core complex, and uncovered its conserved biochemical and structural characteristics common to all other SNAREs. In all, our findings reveal three distinct states of Syntaxin17, and provide mechanistic insights into the Syntaxin17-mediated autophagosome-lysosome fusion process.

PubMed: 32817423
DOI: 10.1073/pnas.2006997117

実験手法

X-RAY DIFFRACTION (2 Å)