Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2'-PO(4) recognition and ADP-ribosylation Journal Article
| Authors: | Banerjee, A.; Munir, A.; Abdullahu, L.; Damha, M. J.; Goldgur, Y.; Shuman, S. |
| Article Title: | Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2'-PO(4) recognition and ADP-ribosylation |
| Abstract: | Tpt1 is an essential agent of fungal tRNA splicing that removes the 2'-PO4 at the splice junction generated by fungal tRNA ligase. Tpt1 catalyzes a unique two-step reaction whereby the 2'-PO4 attacks NAD+ to form an RNA-2'-phospho-ADP-ribosyl intermediate that undergoes transesterification to yield 2'-OH RNA and ADP-ribose-1′′,2′′-cyclic phosphate products. Because Tpt1 is inessential in exemplary bacterial and mammalian taxa, Tpt1 is seen as an attractive antifungal target. Here we report a 1.4 Å crystal structure of Tpt1 in a product-mimetic complex with ADP-ribose-1′′-phosphate in the NAD+ site and pAp in the RNA site. The structure reveals how Tpt1 recognizes a 2'-PO4 RNA splice junction and the mechanism of RNA phospho-ADP-ribosylation. This study also provides evidence that a bacterium has an endogenous phosphorylated substrate with which Tpt1 reacts. |
| Journal Title: | Nature Communications |
| Volume: | 10 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-01-15 |
| Start Page: | 218 |
| Language: | English |
| DOI: | 10.1038/s41467-018-08211-9 |
| PUBMED: | 30644400 |
| PROVIDER: | scopus |
| PMCID: | PMC6333775 |
| DOI/URL: | |
| Notes: | Export Date: 1 February 2019 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work