6GBS

Crystal Structure of the C. themophilum Scavenger Decapping Enzyme DcpS apo form

6GBS の概要

• エントリーDOI: 10.2210/pdb6gbs/pdb
• 分子名称: Putative mRNA decapping protein, 1,2-ETHANEDIOL, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: mrna decapping, decapping enzyme, scavenger decapping enzyme, hydrolase
• 由来する生物種: Chaetomium thermophilum var. thermophilum DSM 1495
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80352.83

構造登録者

Fuchs, A.-L.,Neu, A.,Sprangers, R. (登録日: 2018-04-16, 公開日: 2019-04-24, 最終更新日: 2024-01-17)

主引用文献

Fuchs, A.L.,Wurm, J.P.,Neu, A.,Sprangers, R.
Molecular basis of the selective processing of short mRNA substrates by the DcpS mRNA decapping enzyme.
Proc.Natl.Acad.Sci.USA, 117:19237-19244, 2020

PubMed Abstract: The 5' messenger RNA (mRNA) cap structure enhances translation and protects the transcript against exonucleolytic degradation. During mRNA turnover, this cap is removed from the mRNA. This decapping step is catalyzed by the Scavenger Decapping Enzyme (DcpS), in case the mRNA has been exonucleolyticly shortened from the 3' end by the exosome complex. Here, we show that DcpS only processes mRNA fragments that are shorter than three nucleotides in length. Based on a combination of methyl transverse relaxation optimized (TROSY) NMR spectroscopy and X-ray crystallography, we established that the DcpS substrate length-sensing mechanism is based on steric clashes between the enzyme and the third nucleotide of a capped mRNA. For longer mRNA substrates, these clashes prevent conformational changes in DcpS that are required for the formation of a catalytically competent active site. Point mutations that enlarge the space for the third nucleotide in the mRNA body enhance the activity of DcpS on longer mRNA species. We find that this mechanism to ensure that the enzyme is not active on translating long mRNAs is conserved from yeast to humans. Finally, we show that the products that the exosome releases after 3' to 5' degradation of the mRNA body are indeed short enough to be decapped by DcpS. Our data thus directly confirms the notion that mRNA products of the exosome are direct substrates for DcpS. In summary, we demonstrate a direct relationship between conformational changes and enzyme activity that is exploited to achieve substrate selectivity.

PubMed: 32723815
DOI: 10.1073/pnas.2009362117

実験手法

X-RAY DIFFRACTION (1.946 Å)