Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme

Fei Teng1,2; Yang Wang2; Ming Liu2; Shuyun Tian1; Goran Stjepanovic2; Ming-Yuan Su1,3,4

2023-09-22

10.1016/j.str.2023.09.002

Structure   Impact Factor & Quartile

0969-2126

1878-4186

CULLIN-RING ligases constitute the largest group of E3 ubiquitin ligases. While some CULLIN family members recruit adapters before engaging further with different substrate receptors, homo-dimeric BTB-Kelch family proteins combine adapter and substrate receptor into a single polypeptide for the CULLIN3 family. However, the entire structural assembly and molecular details have not been elucidated to date. Here, we present a cryo-EM structure of the CULLIN3 in complex with Kelch-like protein 22 (KLHL22) and a mitochondrial glutamate dehydrogenase complex I (GDH1) at 3.06 Å resolution. The structure adopts a W-shaped architecture formed by E3 ligase dimers. Three CULLIN3 dimers were found to be dynamically associated with a single GDH1 hexamer. CULLIN3 ligase mediated the polyubiquitination of GDH1 in vitro. Together, these results enabled the establishment of a structural model for understanding the complete assembly of BTB-Kelch proteins with CULLIN3 and how together they recognize oligomeric substrates and target them for ubiquitination.

cryo-EM CULLIN3-RING ubiquitin ligase ubiquitination

SCI

English

First ; Corresponding

BIOLOGY & BIOCHEMISTRY

2-s2.0-85174726446

人工提交

1.Department of Biochemistry, School of Medicine, Southern University of Science and Technology
2.Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong
3.Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology
4.Institute for Biological Electron Microscopy, Southern University of Science and Technology

Fei Teng,Yang Wang,Ming Liu,et al. Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme[J]. Structure,2023,31(31):1-10.

Fei Teng,Yang Wang,Ming Liu,Shuyun Tian,Goran Stjepanovic,&Ming-Yuan Su.(2023).Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme.Structure,31(31),1-10.

Fei Teng,et al."Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme".Structure 31.31(2023):1-10.