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
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机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Dai, Jixun
[1
]
Ambrus, Attila
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h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Ambrus, Attila
[1
]
Hurley, Laurence H.
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机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA
Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA
Univ Arizona, Dept Chem, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Hurley, Laurence H.
[1
,2
,3
,4
]
Yang, Danzhou
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h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA
Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA
Univ Arizona, Dept Chem, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
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
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.