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
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MSK Authors
  1. Stewart H Shuman
    448 Shuman
  2. Yehuda Goldgur
    24 Goldgur
  3. Annum   Munir
    5 Munir