Purine-rich regions in DNA and RNA may contain both guanines and adenines, which have various biological functions. Here we report the crystal structure of an RNA purine-rich fragment containing both guanine and adenine at 1.4 Å resolution. Adenines form an adenine tetrad in the N6-H...N7 conformation. Substitution of an adenine tetrad in the guanine tetraplex does not change the global conformation but introduces irregularity in both the hydrogen bonding interaction pattern in the groove and the metal ion binding pattern in the central cavity of the tetraplex. The irregularity in groove binding may be critical for specific binding in tetraplexes. The formation of G-U octads provides a mechanism for interaction in the groove. Ba2+ ions prefer to bind guanine tetrads, and adenine tetrads can only be bound by Na+ ions, illustrating the binding selectivity of metal ions for the tetraplex.
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We greatly thank Dr. R.V. Hosur for his helpful discussion on the A tetrad conformations in NMR studies and Drs. Florante A. Quiocho and Alex Nickitendo for providing the new version of the CHAIN program. We acknowledge the support of this work by the National Institutes of Health grant GM-17378 and the Board of Regents of Ohio for an Ohio Eminent Scholar Chair and Endowment to M.S. Use of the Advanced Photon Sources was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109-Eng-38.