Unusual DNA Conformation at Low pH Revealed by NMR: Parallel-Stranded DNA Duplex with Homo Base Pairs

Howard Robinson, Andrew H.J. Wang, Gijs A. van der Marel, Jacques H. van Boom

研究成果: 雜誌貢獻文章同行評審

85 引文 斯高帕斯(Scopus)

摘要

We have investigated the conformational potentials of several DNA oligonucleotides containing sequences related to 5ʹ-CGA in neutral pH and low pH (<5.0) conditions. One-dimensional proton NMR spectra show that d(CGATCG), d(TCGATCGA), and d(CGATCGATCG) exhibit new sets of resonances at low pH (~3.8-4.4), when compared to those from the neutral pH samples. The low pH form and the neutral pH form are in slow equilibrium. Analyses of the data suggest that these sequences under low pH conditions adopt structures distinct from B-DNA. Two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) data from the DNA hexamer d(CGATCG) of the neutral and low pH samples were used to analyze their respective structures in solution. An iterative NOE spectral-driven refinement procedure, SPEDREF [Robinson, H., & Wang, A.H.-J. (1992) Biochemistry 31, 3524-3533], was used to show that the neutral pH structure is close to canonical B-DNA. In contrast, analysis of the low pH form using the 2D NOESY data suggests that its structure is consistent with a right-handed parallel-stranded (PS) double helix with symmetrical non-Watson-Crick (C+:C, G:G, A:A, T:T) homo base pairs. Supporting evidence for the PS helix includes the asymmetric inversion-recovery relaxation times associated with the two ends of the helix. The structure is favored by the 5ʹ-CGA sequence in which the cytosines provide the C+:C pairing for the nucleation step and the GpA step is significantly stabilized by the interstrand G-A stacking interactions. This new and unusual structure is different from any of the parallel-stranded structures previously described, and it may have biological roles, such as in DNA recombination or in RNA structures.

原文英語
頁(從 - 到)10510-10517
頁數8
期刊Biochemistry
31
發行號43
DOIs
出版狀態已發佈 - 2月 1 1992
對外發佈

ASJC Scopus subject areas

  • 生物化學

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