MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate

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Title
MUL1-RING recruits the substrate, p53-TAD as a complex with UBE2D2-UB conjugate
Author(s)
Min-Sung Lee; Sang-Ok Lee; J Choi; Minju Ryu; Mi-Kyung Lee; J H Kim; E Hwang; C K Lee; Seung-Wook Chi; K S Ryu
Bibliographic Citation
FEBS Journal, vol. 289, no. 12, pp. 3568-3586
Publication Year
2022
Abstract
The RING domain of MUL1 (RINGMUL1 ) alone mediates ubiquitylation of the p53-transactivation domain (TADp53 ). To elucidate the mechanism underlying the simultaneous recruitment of UBE2D2 and the substrate TADp53 by RINGMUL1 , we determined the complex structure of RINGMUL1 :UBE2D2 and studied the interaction between RINGMUL1 and TADp53 in the presence of UBE2D2-UB thioester (UBE2D2~UB) mimetics. The RINGMUL1 -binding induced the closed conformation of UBE2D2S22R/C85S -UBK48R oxyester (UBE2D2RS -UBROE ), and strongly accelerated its hydrolysis, which was suppressed by the additional N77A-mutation of UBE2D2. Interestingly, UBE2D2S22R/N77A/C85S -UBK48R oxyester (UBE2D2RAS -UBROE ) already formed a closed conformation in the absence of RINGMUL1 . Although TADp53 exhibited weak binding for RINGMUL1 or UBE2D2 alone, its binding affinity was enhanced and even further for RINGMUL1 :UBE2D2 and RINGMUL1 :UBE2D2RAS -UBROE , respectively. The recognition of TADp53 by RINGMUL1 as a complex with UBE2D2~UB is related to the multivalency of the binding events and underlies the ability of RINGMUL1 to ubiquitylate the intrinsically disordered protein, TADp53.
Keyword
p53 transactivation domainUBE2D2UbiquitinMUL1 RING domainNMR
ISSN
1742-464X
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/febs.16360
Type
Article
Appears in Collections:
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > 1. Journal Articles
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