1NA2

Solution structure of the p2b hairpin from human telomerase RNA

1NA2 の概要

• エントリーDOI: 10.2210/pdb1na2/pdb
• NMR情報: BMRB: 5632
• 分子名称: telomerase RNA p2b hairpin (1 entity in total)
• 機能のキーワード: u-u base pair, u-c base pair, pentaloop, hairpin, rna, telomerase, narrow minor groove, u tracts
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9449.54

構造登録者

Theimer, C.A.,Finger, L.D.,Trantirek, L.,Feigon, J. (登録日: 2002-11-26, 公開日: 2003-01-21, 最終更新日: 2024-05-22)

主引用文献

Theimer, C.A.,Finger, L.D.,Trantirek, L.,Feigon, J.
Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA
Proc.Natl.Acad.Sci.USA, 100:449-454, 2003

PubMed Abstract: Autosomal dominant dyskeratosis congenita (DKC), as well as aplastic anemia, has been linked to mutations in the RNA component of telomerase, the ribonucleoprotein responsible for telomere maintenance. Here we examine the effect of the DKC mutations on the structure and stability of human telomerase RNA pseudoknot and CR7 domains by using NMR and thermal melting. The CR7 domain point mutation decreases stability and alters a conserved secondary structure thought to be involved in human telomerase RNA accumulation in vivo. We find that pseudoknot constructs containing the conserved elements of the pseudoknot domain are in equilibrium with a hairpin conformation. The solution structure of the wild-type hairpin reveals that it forms a continuous helix containing a novel run of three consecutive U.U and a U.C base pairs closed by a pentaloop. The six base pairs unique to the hairpin conformation are phylogenetically conserved in mammals, suggesting that this conformation is also functionally important. The DKC mutation in the pseudoknot domain results in a shift in the equilibrium toward the hairpin form, primarily due to destabilization of the pseudoknot. Our results provide insight into the effect of these mutations on telomerase structure and suggest that the catalytic cycle of telomerase involves a delicate interplay between RNA conformational states, alteration of which leads to the disease state.

PubMed: 12525685
DOI: 10.1073/pnas.242720799

実験手法

SOLUTION NMR