Centromeric pyrimidine strands fold into an intercalated motif by forming a double hairpin with a novel T:G:G:T tetrad: Solution structure of the d(TCCCGTTTCCA) dimer

Centromeric pyrimidine strands fold into an intercalated motif by forming a double hairpin with a novel T:G:G:T tetrad: Solution structure of the d(TCCCGTTTCCA) dimer
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DOI:
10.1006/jmbi.1997.1361
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发表时间:
1997-11-07
影响因子:
5.6
通讯作者:
Reid, BR
Reid, BR
中科院分区:
生物学2区
文献类型:
--
作者:
Gallego, J;Chou, SH;Reid, BR

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寡脱氧核苷酸 d(CCCCGTTTCC) 和 d(TCCCGTTTTCCA) 的溶液结构已通过二维 NMR 光谱确定。这些寡聚体是人类着丝粒 α 卫星中 DNA 盒的一部分,由着丝粒蛋白 B (CENP-B) 靶向。 CENP-B 及其在 alpoid DNA 中的识别盒在哺乳动物中都是保守的,这表明其具有重要的生物学作用。在酸性 pH 条件下,d(CCCCGTTTCC)、d(TCCCGTTTCCA) 和完整的 d(TCCCGTTTCCAACGAAG) CENP-B 盒链在溶液中全部折叠并二聚化,形成稳定的双分子结构,其中包含两个 GTTT 发夹环,通过新型 T:G:G:T 四分体相互作用。二聚体的茎区是一个少链嵌入基序,其中发夹单体是平行的,并通过 C:C+ 氢键和嵌入结合在一起。这些环位于二聚体的同一端,并横跨四聚体的窄槽。它们通过碱基交叉堆叠、糖碱基堆叠以及平行 G:G 和反平行 G:T 配对而具有显着的结构和稳定性。在 d(TCCCGTTTCCA)(2) 结构中,插入基序在二聚体的另一端延续,具有未配对但堆叠的腺嘌呤和胸腺嘧啶碱基。讨论了这些结构可能的生物学意义。 (C) 1997 学术出版社有限公司。
The solution structures of the oligodeoxynucleotides d(CCCGTTTCC) and d(TCCCGTTTCCA) have been determined by two-dimensional NMR spectroscopy. These oligomers are part of a DNA box in human centromeric alpha satellite targeted by the centromere protein B (CENP-B). Both CENP-B and its recognition box in alphoid DNA are conserved in mammals, suggesting import-ant biological role. At acidic pH, d(CCCGTTTCC), d(TCCCGTTTCCA) and the full d(TCCCGTTTCCAACGAAG) CENP-B box strand all fold and dimerize in solution forming a stable bimolecular structure containing two GTTT hairpin loops that interact through a novel T:G:G:T tetrad. The stem region of the dimer is a few-stranded intercalated motif in which the hairpin monomers are parallel and held together by C:C+ hydrogen-bonding and intercalation. The loops are at the same end of the dimer and lie across the narrow grooves of the tetraplex. They are remarkably structured and stabilized by base-base cross-stacking, sugar-base stacking, and parallel G:G and antiparallel G:T pairing. In the d(TCCCGTTTCCA)(2) structure, the intercalated motif is continued at the other end of the dimer with unpaired but stacked adenine and thymine bases. The possible biological implications of these structures are discussed. (C) 1997 Academic Press Limited.