8GCB

Structure of RNF125 in complex with a UbcH5b~Ub conjugate

Summary for 8GCB

• Entry DOI: 10.2210/pdb8gcb/pdb
• Descriptor: Ubiquitin-conjugating enzyme E2 D2, E3 ubiquitin-protein ligase RNF125, ZINC ION (3 entities in total)
• Functional Keywords: ubiquitin ring e3 ligase ubiquitin conjugating enzyme complex, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28756.09

Authors

Middleton, A.J.,Day, C.L.,Fokkens, T.J. (deposition date: 2023-03-01, release date: 2023-07-19, Last modification date: 2023-10-18)

Primary citation

Middleton, A.J.,Barzak, F.M.,Fokkens, T.J.,Nguyen, K.,Day, C.L.
Zinc finger 1 of the RING E3 ligase, RNF125, interacts with the E2 to enhance ubiquitylation.
Structure, 31:1208-1219.e5, 2023

PubMed Abstract: Inflammation is essential for healthy immune function, wound healing, and resolution of infection. RIG-I is a key RNA sensor that initiates an immune response, with activation and termination of RIG-I signaling reliant on its modification with ubiquitin. The RING E3 ubiquitin ligase, RNF125, has a critical role in the attenuation of RIG-I signaling, yet it is not known how RNF125 promotes ubiquitin transfer or how its activity is regulated. Here we show that the E3 ligase activity of RNF125 relies on the first zinc finger (ZF1) as well as the RING domain. Surprisingly, ZF1 helps recruit the E2, while residues N-terminal to the RING domain appear to activate the E2∼Ub conjugate. These discoveries help explain how RNF125 brings about the termination of RIG-I dependent inflammatory responses, and help account for the contribution of RNF125 to disease. This study also reveals a new role for ZF domains in E3 ligases.

PubMed: 37541247
DOI: 10.1016/j.str.2023.07.007

Experimental method

X-RAY DIFFRACTION (2.39 Å)