5WWX

Crystal structure of the KH2 domain of human RNA-binding E3 ubiquitin-protein ligase MEX-3C complex with RNA

5WWX の概要

• エントリーDOI: 10.2210/pdb5wwx/pdb
• 関連するPDBエントリー: 5WWW 5WWZ
• 分子名称: RNA-binding E3 ubiquitin-protein ligase MEX3C, RNA (5'-R(P*AP*GP*AP*GP*U)-3'), NICKEL (II) ION, ... (4 entities in total)
• 機能のキーワード: kh2, mex-3c, rna, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q5U5Q3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11440.95

構造登録者

Yang, L.,Wang, C.,Li, F.,Gong, Q. (登録日: 2017-01-05, 公開日: 2017-08-23, 最終更新日: 2023-11-22)

主引用文献

Yang, L.,Wang, C.,Li, F.,Zhang, J.,Nayab, A.,Wu, J.,Shi, Y.,Gong, Q.
The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3-recognition element (MRE) motif with high affinity
J. Biol. Chem., 292:16221-16234, 2017

PubMed Abstract: MEX-3 is a K-homology (KH) domain-containing RNA-binding protein first identified as a translational repressor in , and its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3'-UTR and post-transcriptional regulation of MEX-3 target transcripts. However, the molecular mechanisms of translational repression and the consensus RNA sequence recognized by the MEX-3C KH domain are unknown. Here, using X-ray crystallography and isothermal titration calorimetry, we investigated the RNA-binding activity and selectivity of human MEX-3C dual KH domains. Our high-resolution crystal structures of individual KH domains complexed with a noncanonical U-rich and a GA-rich RNA sequence revealed that the KH1/2 domains of human MEX-3C bound MRE10, a 10-mer RNA (5'-CAGAGUUUAG-3') consisting of an eight-nucleotide MEX-3-recognition element (MRE) motif, with high affinity. Of note, we also identified a consensus RNA motif recognized by human MEX-3C. The potential RNA-binding sites in the 3'-UTR of the human leukocyte antigen serotype () mRNA were mapped with this RNA-binding motif and further confirmed by fluorescence polarization. The binding motif identified here will provide valuable information for future investigations of the functional pathways controlled by human MEX-3C and for predicting potential mRNAs regulated by this enzyme.

PubMed: 28808060
DOI: 10.1074/jbc.M117.797746

実験手法

X-RAY DIFFRACTION (2 Å)