Structural insights to how mammalian capping enzyme reads the CTD code

By Agnidipta Ghosh, Stewart Shuman, C. Lima. 2011

101 citations recorded by the source corpus.

Summary Physical interaction between the phosphorylated RNA polymerase II carboxyl-terminal domain (CTD) and cellular capping enzymes is required for efficient formation of the 5' mRNA cap, the first modification of nascent mRNA. Here we report the crystal structure of the RNA guanylyltransferase component of mammalian capping enzyme (Mce) bound to a CTD phosphopeptide. The CTD adopts an extended β-like conformation that docks Tyr1 and Ser5-PO4 onto the Mce nucleotidyltransferase domain. Structure-guided mutational analysis verified that the Mce-CTD interface is a tunable determinant of CTD binding and stimulation of guanylyltransferase activity, and of Mce function in vivo. The location and composition of the CTD binding site on mammalian capping enzyme is distinct from that of a yeast capping enzyme that recognizes the same CTD primary structure. Thus, capping enzymes from different taxa have evolved different strategies to read the CTD code.

Subfields: Molecular Biology

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In Molecular Biology

1. Jing-Ping Hsin
2. G. B. Robb
3. J. Manley
4. Siu-Hong Chan
5. Anand Ramanathan

Citations in the corpus

• mRNA capping: biological functions and applications (2016, background): “Although the interaction between Ceg1 and the phosphorylated RNAP II CTD has been wellstudied (16,19), the cryo-EM study showed that Cet1 also forms extensive interactions with the transcribing RNA polymerase II complex outside of CTD.”
• The RNA polymerase II CTD coordinates transcription and RNA processing. (2012, background): “This domain has two binding sites for phosphorylated CTD: one specific for the Ser2 phosphorylated CTD and the other, an allosteric activator site, for the Ser5 phosphorylated CTD (Ho and Shuman 1999), which stimulates formation of the enzyme–GMP intermediate (Ho and Shuman 1999; Ghosh et al. 2011).”