Fission yeast RNA triphosphatase reads an Spt5 CTD code Journal Article


Authors: Doamekpor, S. K.; Schwer, B.; Sanchez, A. M.; Shuman, S.; Lima, C. D.
Article Title: Fission yeast RNA triphosphatase reads an Spt5 CTD code
Abstract: mRNA capping enzymes are directed to nascent RNA polymerase II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide motif TPAWNSGSK. Here we report the crystal structure of a Pct1•Spt5-CTD complex, which revealed two CTD docking sites on the Pct1 homodimer that engage TPAWN segments of the motif. Each Spt5 CTD interface, composed of elements from both subunits of the homodimer, is dominated by van der Waals contacts from Pct1 to the tryptophan of the CTD. The bound CTD adopts a distinctive conformation in which the peptide backbone makes a tight U-turn so that the proline stacks over the tryptophan. We show that Pct1 binding to Spt5 CTD is antagonized by threonine phosphorylation. Our results fortify an emerging concept of an "Spt5 CTD code" in which (i) the Spt5 CTD is structurally plastic and can adopt different conformations that are templated by particular cellular Spt5 CTD receptor proteins; and (ii) threonine phosphorylation of the Spt5 CTD repeat inscribes a binary on -off switch that is read by diverse CTD receptors, each in its own distinctive manner.
Keywords: protein phosphorylation; nonhuman; protein motif; phosphatase; transcription; crystal structure; threonine; crystallization; genetic code; schizosaccharomyces; schizosaccharomycetaceae; tryptophan; x-ray crystallography; enzyme active site; mrna capping; elongation; homodimer; mrna processing; rna conformation; fungal rna; article; spt5 ctd code
Journal Title: RNA
Volume: 21
Issue: 1
ISSN: 1355-8382
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2015-01-01
Start Page: 113
End Page: 123
Language: English
DOI: 10.1261/rna.048181.114
PROVIDER: scopus
PMCID: PMC4274631
PUBMED: 25414009
DOI/URL:
Notes: Export Date: 2 February 2015 -- Source: Scopus
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  1. Stewart H Shuman
    546 Shuman
  2. Christopher D Lima
    103 Lima