Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA

Nat Struct Mol Biol. 2010 Apr;17(4):513-8. doi: 10.1038/nsmb.1777. Epub 2010 Mar 28.

Abstract

Telomerase is a specialized DNA polymerase that extends the 3' ends of eukaryotic linear chromosomes, a process required for genomic stability and cell viability. Here we present the crystal structure of the active Tribolium castaneum telomerase catalytic subunit, TERT, bound to an RNA-DNA hairpin designed to resemble the putative RNA-templating region and telomeric DNA. The RNA-DNA hybrid adopts a helical structure, docked in the interior cavity of the TERT ring. Contacts between the RNA template and motifs 2 and B' position the solvent-accessible RNA bases close to the enzyme active site for nucleotide binding and selectivity. Nucleic acid binding induces rigid TERT conformational changes to form a tight catalytic complex. Overall, TERT-RNA template and TERT-telomeric DNA associations are remarkably similar to those observed for retroviral reverse transcriptases, suggesting common mechanistic aspects of DNA replication between the two families of enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalytic Domain
  • DNA / metabolism*
  • Models, Molecular
  • Protein Conformation
  • RNA / metabolism*
  • Telomerase / metabolism*
  • Telomere*
  • Templates, Genetic*
  • Tribolium / enzymology

Substances

  • RNA
  • DNA
  • Telomerase

Associated data

  • PDB/3KYL