8W6A

Crystal structure of TAX1BP1 LIR region in complex with GABARAP

8W6A の概要

• エントリーDOI: 10.2210/pdb8w6a/pdb
• 分子名称: Gamma-aminobutyric acid receptor-associated protein, Tax1-binding protein 1 (3 entities in total)
• 機能のキーワード: atg8, autophagy, protein binding
• 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: 68206.02

構造登録者

Zhang, M.F.,Pan, L.F. (登録日: 2023-08-28, 公開日: 2024-07-10)

主引用文献

Zhang, M.,Wang, Y.,Gong, X.,Wang, Y.,Zhang, Y.,Tang, Y.,Zhou, X.,Liu, H.,Huang, Y.,Zhang, J.,Pan, L.
Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins.
Proc.Natl.Acad.Sci.USA, 121:e2315550121-e2315550121, 2024

PubMed Abstract: TAX1BP1, a multifunctional autophagy adaptor, plays critical roles in different autophagy processes. As an autophagy receptor, TAX1BP1 can interact with RB1CC1, NAP1, and mammalian ATG8 family proteins to drive selective autophagy for relevant substrates. However, the mechanistic bases underpinning the specific interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins remain elusive. Here, we find that there are two distinct binding sites between TAX1BP1 and RB1CC1. In addition to the previously reported TAX1BP1 SKICH (skeletal muscle and kidney enriched inositol phosphatase (SKIP) carboxyl homology)/RB1CC1 coiled-coil interaction, the first coiled-coil domain of TAX1BP1 can directly bind to the extreme C-terminal coiled-coil and Claw region of RB1CC1. We determine the crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex and unravel the detailed binding mechanism of TAX1BP1 SKICH with RB1CC1. Moreover, we demonstrate that RB1CC1 and NAP1 are competitive in binding to the TAX1BP1 SKICH domain, but the presence of NAP1's FIP200-interacting region (FIR) motif can stabilize the ternary TAX1BP1/NAP1/RB1CC1 complex formation. Finally, we elucidate the molecular mechanism governing the selective interactions of TAX1BP1 with ATG8 family members by solving the structure of GABARAP in complex with the non-canonical LIR (LC3-interacting region) motif of TAX1BP1, which unveils a unique binding mode between LIR and ATG8 family protein. Collectively, our findings provide mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins and are valuable for further understanding the working mode and function of TAX1BP1 in autophagy.

PubMed: 38437556
DOI: 10.1073/pnas.2315550121

実験手法

X-RAY DIFFRACTION (1.53 Å)