6TRQ
S.c. Scavenger Decapping Enzyme DcpS in complex with the capped RNA dinucleotide m7G-GU
Summary for 6TRQ
| Entry DOI | 10.2210/pdb6trq/pdb |
| Descriptor | m7GpppX diphosphatase, PHOSPHONATE, URIDINE-5'-MONOPHOSPHATE, ... (7 entities in total) |
| Functional Keywords | mrna decapping, mrna degradation, decapping, hydrolase |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) |
| Total number of polymer chains | 4 |
| Total formula weight | 163486.89 |
| Authors | Fuchs, A.-L.,Neu, A.,Sprangers, R. (deposition date: 2019-12-19, release date: 2020-07-22, Last modification date: 2024-03-06) |
| Primary citation | 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 Cited by 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: 32723815DOI: 10.1073/pnas.2009362117 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.944 Å) |
Structure validation
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