School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore.
J Am Chem Soc. 2012 Apr 4;134(13):5807-16. doi: 10.1021/ja208993r. Epub 2012 Mar 26.
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 A·T Watson-Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplexstructure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.
CEB25 是一个人类的微卫星基因座，由略有多态性的 52 个核苷酸（nt）串联重复组成。从遗传学角度来看，人类群体中的大多数（如果不是全部）个体都是杂合子，携带从 0.5 到 20 kb 不等的等位基因，这些等位基因通过孟德尔遗传方式得以维持，但也受到种系不稳定的影响。为了深入了解 CEB25 的生物学作用，我们对其结构特征进行了研究。我们报告了 CEB25 基序中保守的 26 个核苷酸富含 G 片段形成的 G-四链体的 NMR 结构。在 K(+)溶液中，该序列形成了一种涉及 9 个核苷酸中央双链反转环的螺旋桨型平行链 G-四链体。这个长环通过一个 A·T Watson-Crick 碱基对和一个潜在的 G·A 非经典碱基对与序列的 5'-末端结合。这些碱基对有助于整个 G-四链体结构的稳定性，如焓增加约 17 kcal/mol 或熔点升高约 6°C 所测量的。此外，我们证明在更长的序列背景下，这种单态结构可以折叠成珍珠项链结构。
