3X1O

Crystal structure of the ROQ domain of human Roquin

3X1O の概要

• エントリーDOI: 10.2210/pdb3x1o/pdb
• 関連するPDBエントリー: 4TXA
• 分子名称: Roquin-1, IODIDE ION (3 entities in total)
• 機能のキーワード: winged-helix motif, rna, cytosol, rna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, P-body : Q5TC82
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50211.59

構造登録者

Ose, T.,Verma, A.,Cockburn, J.B.,Berrow, N.S.,Alderton, D.,Stuart, D.,Owens, R.J.,Jones, E.Y. (登録日: 2014-11-26, 公開日: 2015-03-11, 最終更新日: 2024-03-20)

主引用文献

Srivastava, M.,Duan, G.,Kershaw, N.J.,Athanasopoulos, V.,Yeo, J.H.,Ose, T.,Hu, D.,Brown, S.H.J.,Jergic, S.,Patel, H.R.,Pratama, A.,Richards, S.,Verma, A.,Jones, E.Y.,Heissmeyer, V.,Preiss, T.,Dixon, N.E.,Chong, M.M.W.,Babon, J.J.,Vinuesa, C.G.
Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis
Nat Commun, 6:6253-6253, 2015

PubMed Abstract: Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquin(san)), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3' end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.

PubMed: 25697406
DOI: 10.1038/ncomms7253

実験手法

X-RAY DIFFRACTION (2.201 Å)