2MPS

Structure of complex of MDM2(3-109) and P73 TAD(10-25)

2MPS の概要

• エントリーDOI: 10.2210/pdb2mps/pdb
• NMR情報: BMRB: 18876
• 分子名称: E3 ubiquitin-protein ligase Mdm2, Tumor protein p73 (2 entities in total)
• 機能のキーワード: mdm2, p73 tad, p53, ligase-peptide complex, ligase/peptide
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus, nucleoplasm: Q00987; Nucleus: O15350
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14067.10

構造登録者

Shin, J.S.,Ha, J.H.,Chi, S.W. (登録日: 2014-06-02, 公開日: 2015-06-03, 最終更新日: 2024-05-15)

主引用文献

Shin, J.S.,Ha, J.H.,Lee, D.H.,Ryu, K.S.,Bae, K.H.,Park, B.C.,Park, S.G.,Yi, G.S.,Chi, S.W.
Structural convergence of unstructured p53 family transactivation domains in MDM2 recognition
Cell Cycle, 14:533-543, 2015

PubMed Abstract: The p53, p63, and p73 proteins belong to the p53 family of transcription factors, which play key roles in tumor suppression. Although the transactivation domains (TADs) of the p53 family are intrinsically disordered, these domains are commonly involved in the regulatory interactions with mouse double minute 2 (MDM2). In this study, we determined the solution structure of the p73TAD peptide in complex with MDM2 using NMR spectroscopy and biophysically characterized the interactions between the p53 family TAD peptides and MDM2. In combination with mutagenesis data, the complex structures revealed remarkably close mimicry of the MDM2 recognition mechanism among the p53 family TADs. Upon binding with MDM2, the intrinsically disordered p73TAD and p63TAD peptides adopt an amphipathic α-helical conformation, which is similar to the conformation of p53TAD, although the α-helical content induced by MDM2 binding varies. With isothermal titration calorimetry (ITC) and circular dichroism (CD) data, our biophysical characterization showed that p73TAD resembles p53TAD more closely than p63TAD in terms of helical stability, MDM2 binding affinity, and phosphorylation effects on MDM2 binding. Therefore, our structural information may be useful in establishing alternative anticancer strategies that exploit the activation of the p73 pathway against human tumors bearing p53 mutations.

PubMed: 25591003
DOI: 10.1080/15384101.2014.998056

実験手法

SOLUTION NMR