1me0
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CHIMERIC HAIRPIN WITH 2',5'-LINKED RNA LOOP AND DNA STEM
OverviewOverview
We have recently shown that hairpins containing 2',5'-linked RNA loops, exhibit superior thermodynamic stability compared to native hairpins, comprised of 3',5'-RNA loops [Hannoush, R. N.; Damha, M. J. J. Am. Chem., Soc. 2001, 123, 12368-12374]. A remarkable feature of the 2',5'-r(UUCG), tetraloop is that, unlike the corresponding 3',5'-linked tetraloop, its, stability is virtually independent of the hairpin stem composition. Here, we determine the solution structure of unusually stable hairpins of the, sequence 5'-G(1)G(2)A(3)C(4)-(U(5)U(6)C(7)G(8))-G(9)(U/T(10))C(11)C(12)-3', containing a 2',5'-linked RNA (UUCG) loop and either an RNA or a DNA stem., The 2',5'-linked RNA loop adopts a new fold that is completely different, from that previously observed for the native 3',5'-linked RNA loop. The, 2',5'-RNA loop is stabilized by (a). U5.G8 wobble base pairing, with both, nucleotide residues in the anti-conformation, (b). extensive base, stacking, and (c). sugar-base and sugar-sugar contacts, all of which, contribute to the extra stability of this hairpin structure. The U5:G8, base pair stacks on top of the C4:G9 loop-closing base pair and thus, appears as a continuation of the stem. The loop uracil U6 base stacks, above U5 base, while the cytosine C7 base protrudes out into the solvent, and does not participate in any of the stabilizing interactions. The, different sugar pucker and intrinsic bonding interactions within the, 2',5'-linked ribonucleotides help explain the unusual stability and, conformational properties displayed by 2',5'-RNA tetraloops. These, findings are relevant for the design of more effective RNA-based aptamers, ribozymes, and antisense agents and identify the 2',5'-RNA loop as a novel, structural motif.
About this StructureAbout this Structure
1ME0 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
A novel RNA motif based on the structure of unusually stable 2',5'-linked r(UUCG) loops., Denisov AY, Hannoush RN, Gehring K, Damha MJ, J Am Chem Soc. 2003 Sep 24;125(38):11525-31. PMID:13129354
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