8W4J

Cryo-EM structure of the KLHL22 E3 ligase bound to human glutamate dehydrogenase I

Summary for 8W4J

• Entry DOI: 10.2210/pdb8w4j/pdb
• EMDB information: 37235 37247 37266
• Descriptor: Glutamate dehydrogenase 1, mitochondrial, Kelch-like protein 22 (2 entities in total)
• Functional Keywords: e3 ligase, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 512373.66

Authors

Su, M.-Y.,Su, M.-Y. (deposition date: 2023-08-24, release date: 2023-11-01, Last modification date: 2023-11-22)

Primary citation

Teng, F.,Wang, Y.,Liu, M.,Tian, S.,Stjepanovic, G.,Su, M.Y.
Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme.
Structure, 31:1431-, 2023

PubMed Abstract: 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.

PubMed: 37788672
DOI: 10.1016/j.str.2023.09.002

Experimental method

ELECTRON MICROSCOPY (3.06 Å)