Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA.
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.
Mitchell
Meghan
M
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Gillis
Andrew
A
Futahashi
Mizuko
M
Fujiwara
Haruhiko
H
Skordalakes
Emmanuel
E
D000818:Animals; D020134:Catalytic Domain; D004247:DNA / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere; D013698:Templates, Genetic; D014231:Tribolium / Q000201:enzymology
D012313:RNA; D004247:DNA; D019098:Telomerase