A Direct and Nondestructive Approach To Determine the Folding Structure of the I-Motif DNA Secondary Structure by NMR

被引:36
作者
Dai, Jixun [1 ]
Ambrus, Attila [1 ]
Hurley, Laurence H. [1 ,2 ,3 ,4 ]
Yang, Danzhou [1 ,2 ,3 ,4 ]
机构
[1] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
[2] Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA
[3] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA
[4] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA
基金
美国国家卫生研究院;
关键词
HUMAN TELOMERIC SEQUENCE; G-QUADRUPLEX STRUCTURE; PROMOTER REGION; NUCLEIC-ACIDS; RICH STRAND; SPIN-ECHO; RNA; STABILIZATION; ASSIGNMENT; FRAGMENT;
D O I
10.1021/ja900967r
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
I-motifs are four-stranded DNA secondary structures formed in C-rich DNA sequences and consist of parallel-stranded DNA duplexes zipped together in an antiparallel orientation by intercalated, hemiprotonated cytosine-cytosine base pairs. I-motif structures have been indicated to form in various regions of the human genome as well as in nanotechnological applications. While NMR is a major toot for structural studies of I-motifs, the determination of the folding topologies of unimolecular I-motifs has been a challenging and arduous task using conventional NMR spectral assignment strategies, due to the inherent sequence redundancy of the C-rich strands in the formation of unimolecular I-motif structures. We report here a direct and nondestructive method that can be utilized to unambiguously determine the hemiprotonated C-C base pairs and thus the folding topology of unimolecular I-motif structures formed from native C-rich DNA sequences. The reported approach uses affordable tow-enrichment site-specific labeling. More significantly, the reported method can directly and unambiguously determine the equilibrating multiple conformations coexisting in a single DNA sequence, which would be a very difficult task using conventional assignment strategies. Additionally, this method can be applied to the direct detection of the base-paired thymines that are involved in the capping structures.
引用
收藏
页码:6102 / +
页数:5
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