6IEH

Crystal structures of the hMTR4-NRDE2 complex

6IEH の概要

• エントリーDOI: 10.2210/pdb6ieh/pdb
• 分子名称: Exosome RNA helicase MTR4, Protein NRDE2 homolog, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: rna helicase, mtr4, nrde2, complex, rna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123617.54

構造登録者

Chen, J.Y.,Yun, C.H. (登録日: 2018-09-14, 公開日: 2019-04-03, 最終更新日: 2023-11-22)

主引用文献

Wang, J.,Chen, J.,Wu, G.,Zhang, H.,Du, X.,Chen, S.,Zhang, L.,Wang, K.,Fan, J.,Gao, S.,Wu, X.,Zhang, S.,Kuai, B.,Zhao, P.,Chi, B.,Wang, L.,Li, G.,Wong, C.C.L.,Zhou, Y.,Li, J.,Yun, C.,Cheng, H.
NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction.
Genes Dev., 33:536-549, 2019

PubMed Abstract: The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.

PubMed: 30842217
DOI: 10.1101/gad.322602.118

実験手法

X-RAY DIFFRACTION (2.892 Å)