PDBsum entry 1xwp

RNA

PDB id: 1xwp

Contents

DNA/RNA

References listed in PDB file

Key reference

Title

Nmr structures of double loops of an RNA aptamer against mammalian initiation factor 4a.

Authors

T.Sakamoto, A.Oguro, G.Kawai, T.Ohtsu, Y.Nakamura.

Ref.

Nucleic Acids Res, 2005, 33, 745-754.

PubMed id

15687383

Abstract

A high affinity RNA aptamer (APT58, 58 nt long) against mammalian initiation factor 4A (eIF4A) requires nearly its entire nucleotide sequence for efficient binding. Since splitting either APT58 or eIF4A into two domains diminishes the affinity for each other, it is suggested that multiple interactions or a global interaction between the two molecules accounts for the high affinity. To understand the structural basis of APT58's global recognition of eIF4A, we determined the solution structure of two essential nucleotide loops (AUCGCA and ACAUAGA) within the aptamer using NMR spectroscopy. The AUCGCA loop is stabilized by a U-turn motif and contains a non-canonical A:A base pair (the single hydrogen bond mismatch: Hoogsteen/Sugar-edge). On the other hand, the ACAUAGA loop is stabilized by an AUA tri-nucleotide loop motif and contains the other type of A:A base pair (single hydrogen bond mismatch: Watson-Crick/Watson-Crick). Considering the known structural and functional properties of APT58, we propose that the AUCGCA loop is directly involved in the interaction with eIF4A, while the flexibility of the ACAUAGA loop is important to support this interaction. The Watson-Crick edges of C7 and C9 in the AUCGCA loop may directly interact with eIF4A.

Figure 3.
Tertiary structures of APT15 and APT16 solved by NMR. (A) A superposition of the final 20 structures of APT15. (B) Stereo view of the minimized average structure of APT15. (C) A superposition of the final 20 structures of APT16. (D) Stereo view of the minimized average structure of the APT16. G, A, U and C residues are colored in blue, red, green and yellow, respectively.

Figure 5.
Structural comparison of the AUCGCA loop of APT15 and the stem-loop IIa in yeast U2 snRNA. (A) The AUCGCA loop structure in APT15. (B) The GUAACA loop structure in loop IIa of U2 snRNA (38). Schematic representations of the (C) AUCGCA loop structure and (D) GUAACA loop structure are shown. In the schematic representations, symbols are used as follows: black rectangle, anti base; open rectangle, syn base; red rectangle, stacking interaction; blue circle, hydrogen bonding interaction; open circle, C3'-endo ribose; open square, C2'-endo ribose.

The above figures are reprinted from an Open Access publication published by Oxford University Press: Nucleic Acids Res (2005, 33, 745-754) copyright 2005.