Structural insights into the ubiquitylation strategy of the oligomeric CRL2^FEM1B E3 ubiquitin ligase

Dai, Zonglin1,2; Liang, Ling1,3; Wang, Weize1,4; Zuo, Peng1,2; Yu, Shang3; Liu, Yaqi5; Zhao, Xuyang1; Lu, Yishuo1,4; Jin, Yan1; Zhang, Fangting6; Ding, Dian1; Deng, Weiwei7; Yin, Yuxin1,2,4,6

2024-03-15

10.1038/s44318-024-00047-y

EMBO JOURNAL   影响因子和分区

0261-4189

1460-2075

Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2(FEM1B) in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2(FEM1B) is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2(FEM1B). Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2(FEM1B) according to substrates with different scales.

Cryo-EM Cullin-RING E3 Ubiquitin Ligase Ubiquitylation Oligomerization

SCI

英语

其他

Queen's University Cancer Research Institute["82030081","81874235"] ; National Natural Science Foundation of China[2021YFA1300601] ; Shenzhen High-level Hospital Construction Fund[JCYJ20220818102811024]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:001220428400010

SPRINGERNATURE

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Peking Univ, Beijing Key Lab Tumor Syst Biol, Sch Basic Med Sci, Inst Syst Biomed,Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Biophys, Beijing 100191, Peoples R China
4.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
5.Columbia Univ Coll Phys & Surg, Dept Med, Clyde & Helen Wu Ctr Mol Cardiol, Dept Physiol & Cellular Biophys, New York, NY 10032 USA
6.Peking Univ, Shenzhen Hosp, Inst Precis Med, Shenzhen 518036, Peoples R China
7.Southern Univ Sci & Technol, Dept Mech & Aerosp Engn, Shenzhen 518055, Peoples R China

Dai, Zonglin,Liang, Ling,Wang, Weize,et al. Structural insights into the ubiquitylation strategy of the oligomeric CRL2^FEM1B E3 ubiquitin ligase[J]. EMBO JOURNAL,2024,43(6).

Dai, Zonglin.,Liang, Ling.,Wang, Weize.,Zuo, Peng.,Yu, Shang.,...&Yin, Yuxin.(2024).Structural insights into the ubiquitylation strategy of the oligomeric CRL2^FEM1B E3 ubiquitin ligase.EMBO JOURNAL,43(6).

Dai, Zonglin,et al."Structural insights into the ubiquitylation strategy of the oligomeric CRL2^FEM1B E3 ubiquitin ligase".EMBO JOURNAL 43.6(2024).