1NA2
Solution structure of the p2b hairpin from human telomerase RNA
Summary for 1NA2
| Entry DOI | 10.2210/pdb1na2/pdb |
| NMR Information | BMRB: 5632 |
| Descriptor | telomerase RNA p2b hairpin (1 entity in total) |
| Functional Keywords | u-u base pair, u-c base pair, pentaloop, hairpin, rna, telomerase, narrow minor groove, u tracts |
| Total number of polymer chains | 1 |
| Total formula weight | 9449.54 |
| Authors | Theimer, C.A.,Finger, L.D.,Trantirek, L.,Feigon, J. (deposition date: 2002-11-26, release date: 2003-01-21, Last modification date: 2024-05-22) |
| Primary citation | 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 Cited by 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: 12525685DOI: 10.1073/pnas.242720799 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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