Summary information and primary citation
- PDB-id
-
6usq;
SNAP-derived features in text and
JSON formats
- Class
- nuclear protein, transferase-RNA-DNA
- Method
- X-ray (3.62 Å)
- Summary
- Telomerase reverse transcriptase binary complex with
y256a mutation, tert:DNA
- Reference
-
Schaich MA, Sanford SL, Welfer GA, Johnson SA, Khoang TH,
Opresko PL, Freudenthal BD (2020): "Mechanisms
of nucleotide selection by telomerase."
Elife, 9. doi: 10.7554/eLife.55438.
- Abstract
- Telomerase extends telomere sequences at chromosomal
ends to protect genomic DNA. During this process it must
select the correct nucleotide from a pool of nucleotides
with various sugars and base pairing properties, which is
critically important for the proper capping of telomeric
sequences by shelterin. Unfortunately, how telomerase
selects correct nucleotides is unknown. Here, we determined
structures of <i>Tribolium castaneum</i>
telomerase reverse transcriptase (TERT) throughout its
catalytic cycle and mapped the active site residues
responsible for nucleoside selection, metal coordination,
triphosphate binding, and RNA template stabilization. We
found that TERT inserts a mismatch or ribonucleotide ~1 in
10,000 and ~1 in 14,000 insertion events, respectively. At
biological ribonucleotide concentrations, these rates
translate to ~40 ribonucleotides inserted per 10 kilobases.
Human telomerase assays determined a conserved tyrosine
steric gate regulates ribonucleotide insertion into
telomeres. Cumulatively, our work provides insight into how
telomerase selects the proper nucleotide to maintain
telomere integrity.
