Structure and mechanism of RNA ligase

Structure. 2004 Feb;12(2):327-39. doi: 10.1016/j.str.2004.01.011.

Abstract

T4 RNA ligase 2 (Rnl2) exemplifies an RNA ligase family that includes the RNA editing ligases (RELs) of Trypanosoma and Leishmania. The Rnl2/REL enzymes are defined by essential signature residues and a unique C-terminal domain, which we show is essential for sealing of 3'-OH and 5'-PO4 RNA ends by Rnl2, but not for ligase adenylation or phosphodiester bond formation at a preadenylated AppRNA end. The N-terminal segment Rnl2(1-249) of the 334 aa Rnl2 protein comprises an autonomous adenylyltransferase/AppRNA ligase domain. We report the 1.9 A crystal structure of the ligase domain with AMP bound at the active site, which reveals a shared fold, catalytic mechanism, and evolutionary history for RNA ligases, DNA ligases, and mRNA capping enzymes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Monophosphate / chemistry*
  • Amino Acid Sequence
  • Animals
  • Bacteriophage T4 / enzymology*
  • Crystallography, X-Ray
  • Leishmania / chemistry
  • Models, Molecular*
  • Molecular Sequence Data
  • Mutation*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Ligase (ATP) / chemistry*
  • Sequence Homology, Amino Acid
  • Trypanosoma / chemistry
  • Viral Proteins / chemistry*

Substances

  • Viral Proteins
  • Adenosine Monophosphate
  • RNA Ligase (ATP)
  • bacteriophage T4 RNA ligase 2

Associated data

  • PDB/1S68