Formation of Pearl-Necklace Monomorphic G-Quadruplexes in the Human CEB25 Minisatellite
Formation of Pearl-Necklace Monomorphic G-Quadruplexes in the Human CEB25 Minisatellite
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DOI：
10.1021/ja208993r
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发表时间：
2012-04-04
影响因子：
15
通讯作者：
Anh Tuan Phan
中科院分区：
文献类型：
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作者：
Amrane, Samir;Adrian, Michael;Anh Tuan Phan
CEB25是一个人类小卫星位点，由52个核苷酸（nt）串联重复序列组成。从遗传学上讲，大多数人（如果不是全部的话）都是杂合的，携带的等位基因范围从0.5到20 kb，由孟德尔遗传维持，但也受到种系不稳定性的影响。为了深入了解CEB25的生物学作用，我们研究了它的结构特征。我们报道了由CEB25基序的保守的26-nt富g片段形成的g -四重体的核磁共振结构。在K+溶液中，该序列形成螺旋桨型平行链g -四联体，包括一个9-nt中心双链反转环。这个长环由一个AT沃森克里克碱基对和一个潜在的ga非规范碱基对锚定在序列的5'端。这些碱基对有助于整个g -四相结构的稳定性，通过增加约17千卡/摩尔的焓或6摄氏度的熔化温度来测量。进一步，我们证明了这种单态结构可以在更长的序列上下文中形成折叠成珍珠项链结构。
CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K+ solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5'-end of the sequence by an AT Watson Crick base pair and a potential G.A. noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplex structure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 degrees C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.