2AU4

Class I GTP aptamer

Summary for 2AU4

• Entry DOI: 10.2210/pdb2au4/pdb
• NMR Information: BMRB: 6814
• Descriptor: Class I RNA aptamer to GTP, GUANOSINE-5'-TRIPHOSPHATE (2 entities in total)
• Functional Keywords: rna, aptamer
• Total number of polymer chains: 1
• Total formula weight: 13847.12

Authors

Carothers, J.M.,Davis, J.H.,Chou, J.J.,Szostak, J.W. (deposition date: 2005-08-26, release date: 2006-03-28, Last modification date: 2024-05-22)

Primary citation

Carothers, J.M.,Davis, J.H.,Chou, J.J.,Szostak, J.W.
Solution structure of an informationally complex high-affinity RNA aptamer to GTP.
Rna, 12:567-579, 2006

PubMed Abstract: Higher-affinity RNA aptamers to GTP are more informationally complex than lower-affinity aptamers. Analog binding studies have shown that the additional information needed to improve affinity does not specify more interactions with the ligand. In light of those observations, we would like to understand the structural characteristics that enable complex aptamers to bind their ligands with higher affinity. Here we present the solution structure of the 41-nt Class I GTP aptamer (K(d) = 75 nM) as determined by NMR. The backbone of the aptamer forms a reverse-S that shapes the binding pocket. The ligand nucleobase stacks between purine platforms and makes hydrogen bonds with the edge of another base. Interestingly, the local modes of interaction for the Class I aptamer and an RNA aptamer that binds ATP with a K(d) of 6 microM are very much alike. The aptamers exhibit nearly identical levels of binding specificity and fraction of ligand sequestered from the solvent (81%-85%). However, the GTP aptamer is more informationally complex (approximately 45 vs. 35 bits) and has a larger recognition bulge (15 vs. 12 nucleotides) with many more stabilizing base-base interactions. Because the aptamers have similar modes of ligand binding, we conclude that the stabilizing structural elements in the Class I aptamer are responsible for much of the difference in K(d). These results are consistent with the hypothesis that increasing the number of intra-RNA interactions, rather than adding specific contacts to the ligand, is the simplest way to improve binding affinity.

PubMed: 16510427
DOI: 10.1261/rna.2251306

Experimental method

SOLUTION NMR