6M2C

Distinct mechanism of MUL1-RING domain simultaneously recruiting E2 enzyme and the substrate p53-TAD domain

Summary for 6M2C

• Entry DOI: 10.2210/pdb6m2c/pdb
• Descriptor: Ubiquitin-conjugating enzyme E2 D2, Mitochondrial ubiquitin ligase activator of NFKB 1, ZINC ION, ... (4 entities in total)
• Functional Keywords: mul1-ring, ube2d2, structural protein, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 92550.10

Authors

Lee, S.O.,Ryu, K.S.,Chi, S.-W. (deposition date: 2020-02-27, release date: 2021-04-07, Last modification date: 2023-11-29)

Primary citation

Lee, M.S.,Lee, S.O.,Choi, J.,Ryu, M.,Lee, M.K.,Kim, J.H.,Hwang, E.,Lee, C.K.,Chi, S.W.,Ryu, K.S.
MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate.
Febs J., 2022

PubMed Abstract: The RING domain of MUL1 (RING ) alone mediates ubiquitylation of the p53-transactivation domain (TAD ). To elucidate the mechanism underlying the simultaneous recruitment of UBE2D2 and the substrate TAD by RING , we determined the complex structure of RING :UBE2D2 and studied the interaction between RING and TAD in the presence of UBE2D2-UB thioester (UBE2D2~UB) mimetics. The RING -binding induced the closed conformation of UBE2D2 -UB oxyester (UBE2D2 -UB ), and strongly accelerated its hydrolysis, which was suppressed by the additional N77A-mutation of UBE2D2. Interestingly, UBE2D2 -UB oxyester (UBE2D2 -UB ) already formed a closed conformation in the absence of RING . Although TAD exhibited weak binding for RING or UBE2D2 alone, its binding affinity was enhanced and even further for RING :UBE2D2 and RING :UBE2D2 -UB , respectively. The recognition of TAD by RING as a complex with UBE2D2~UB is related to the multivalency of the binding events and underlies the ability of RING to ubiquitylate the intrinsically disordered protein, TAD .

PubMed: 35048531
DOI: 10.1111/febs.16360

Experimental method

X-RAY DIFFRACTION (2.702 Å)