4pz6 | pdb_00004pz6
PCE1 guanylyltransferase bound to SER2/SER5 phosphorylated RNA pol II CTD
Structural highlights
FunctionMCE1_SCHPO Second step of mRNA capping. Transfer of the GMP moiety of GTP to the 5'-end of RNA via an enzyme-GMP covalent reaction intermediate (By similarity). Publication Abstract from PubMedInteractions between RNA guanylyltransferase (GTase) and the C-terminal domain (CTD) repeats of RNA polymerase II (Pol2) and elongation factor Spt5 are thought to orchestrate cotranscriptional capping of nascent mRNAs. The crystal structure of a fission yeast GTase*Pol2 CTD complex reveals a unique docking site on the nucleotidyl transferase domain for an 8-amino-acid Pol2 CTD segment, S5PPSYSPTS5P, bracketed by two Ser5-PO4 marks. Analysis of GTase mutations that disrupt the Pol2 CTD interface shows that at least one of the two Ser5-PO4-binding sites is required for cell viability and that each site is important for cell growth at 37 degrees C. Fission yeast GTase binds the Spt5 CTD at a separate docking site in the OB-fold domain that captures the Trp4 residue of the Spt5 nonapeptide repeat T(1)PAW(4)NSGSK. A disruptive mutation in the Spt5 CTD-binding site of GTase is synthetically lethal with mutations in the Pol2 CTD-binding site, signifying that the Spt5 and Pol2 CTDs cooperate to recruit capping enzyme in vivo. CTD phosphorylation has opposite effects on the interaction of GTase with Pol2 (Ser5-PO4 is required for binding) versus Spt5 (Thr1-PO4 inhibits binding). We propose that the state of Thr1 phosphorylation comprises a binary "Spt5 CTD code" that is read by capping enzyme independent of and parallel to its response to the state of the Pol2 CTD. How an mRNA capping enzyme reads distinct RNA polymerase II and Spt5 CTD phosphorylation codes.,Doamekpor SK, Sanchez AM, Schwer B, Shuman S, Lima CD Genes Dev. 2014 Jun 15;28(12):1323-36. doi: 10.1101/gad.242768.114. PMID:24939935[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
