Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52

被引：30

作者：

Fu, Tao ^{[1
]}

Zhang, Mingfang ^{[1
]}

Zhou, Zixuan ^{[1
]}

Wu, Ping ^{[2
]}

Peng, Chao ^{[2
]}

Wang, Yingli ^{[1
]}

Gong, Xinyu ^{[1
]}

Li, Ying ^{[1
]}

Wang, Yaru ^{[1
]}

Xu, Xiaolong ^{[1
]}

Li, Miao ^{[3
]}

Shen, Liqiang ^{[3
]}

Pan, Lifeng ^{[1
,3
]}

机构：

[1] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Ctr Excellence Mol Synth,State Key Lab Bioorgan, Shanghai 200032, Peoples R China

[2] Chinese Acad Sci, Zhangjiang Lab, Shanghai Adv Res Inst, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China

[3] Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Chem & Mat Sci, 1 Sub Lane Xiangshan, Hangzhou 310024, Peoples R China

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 33期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

ENDOPLASMIC-RETICULUM TURNOVER; SELECTIVE AUTOPHAGY; UBIQUITIN RECOGNITION; MOLECULAR-BASIS; MYOSIN-VI; PHOSPHORYLATION; OPTINEURIN; BINDING; FIP200; MECHANISMS;

D O I：

10.1126/sciadv.abi6582

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The recruitment of Unc-51-like kinase and TANK-binding kinase 1 complexes is essential for Nuclear dot protein 52-mediated selective autophagy and relies on the specific association of NDP52, RB1-inducible coiled-coil protein 1, and Nak-associated protein 1 (5-azacytidine-induced protein 2, AZI2). However, the underlying molecular mechanism remains elusive. Here, we find that except for the NDP52 SKIP carboxyl homology (SKICH)/RB1CC1 coiledcoil interaction, the LC3-interacting region of NDP52 can directly interact with the RB1CC1 Claw domain, as that of NAP1 FIP200-binding region (FIR). The determined crystal structures of NDP52 SKICH/RB1CC1 complex, NAP1 FIR/RB1CC1 complex, and the related NAP1 FIR/Gamma-aminobutyric acid receptor-associated protein complex not only elucidate the molecular bases underpinning the interactions of RB1CC1 with NDP52 and NAP1 but also reveal that RB1CC1 Claw and Autophagy-related protein 8 family proteins are competitive in binding to NAP1 and NDP52. Overall, our findings provide mechanistic insights into the interactions of NDP52, NAP1 with RB1CC1 and ATG8 family proteins.

引用

页数：16

共 60 条

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