5JP4

Crystal structure of S. pombe Dcp1 in complex with the decapping enhancer EDC

5JP4 の概要

• エントリーDOI: 10.2210/pdb5jp4/pdb
• 分子名称: mRNA-decapping enzyme subunit 1, Uncharacterized protein C18G6.09c (3 entities in total)
• 機能のキーワード: evh1, complex, mrna, decapping, hydrolase, peptide binding protein
• 由来する生物種: Schizosaccharomyces pombe (Fission yeast); 詳細
• 細胞内の位置: Cytoplasm : Q9P805
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19342.84

構造登録者

Wurm, J.P.,Sprangers, R. (登録日: 2016-05-03, 公開日: 2016-06-01, 最終更新日: 2024-02-07)

主引用文献

Wurm, J.P.,Overbeck, J.,Sprangers, R.
The S. pombe mRNA decapping complex recruits cofactors and an Edc1-like activator through a single dynamic surface.
Rna, 22:1360-1372, 2016

PubMed Abstract: The removal of the 5' 7-methylguanosine mRNA cap structure (decapping) is a central step in the 5'-3' mRNA degradation pathway and is performed by the Dcp1:Dcp2 decapping complex. The activity of this complex is tightly regulated to prevent premature degradation of the transcript. Here, we establish that the aromatic groove of the EVH1 domain of Schizosaccharomyces pombe Dcp1 can interact with proline-rich sequences in the exonuclease Xrn1, the scaffolding protein Pat1, the helicase Dhh1, and the C-terminal disordered region of Dcp2. We show that this region of Dcp1 can also recruit a previously unidentified enhancer of decapping protein (Edc1) and solved the crystal structure of the complex. NMR relaxation dispersion experiments reveal that the Dcp1 binding site can adopt multiple conformations, thus providing the plasticity that is required to accommodate different ligands. We show that the activator Edc1 makes additional contacts with the regulatory domain of Dcp2 and that an activation motif in Edc1 increases the RNA affinity of Dcp1:Dcp2. Our data support a model where Edc1 stabilizes the RNA in the active site, which results in enhanced decapping rates. In summary, we show that multiple decapping factors, including the Dcp2 C-terminal region, compete with Edc1 for Dcp1 binding. Our data thus reveal a network of interactions that can fine-tune the catalytic activity of the decapping complex.

PubMed: 27354705
DOI: 10.1261/rna.057315.116

実験手法

X-RAY DIFFRACTION (2.043 Å)