Recognition and binding of human telomeric G-quadruplex DNA by unfolding protein 1.
Recognition and binding of human telomeric G-quadruplex DNA by unfolding protein 1.
复制标题
DOI：
10.1021/bi500351u
复制
发表时间：
2014-05-27
期刊：
影响因子：
2.9
通讯作者：
Graves D
中科院分区：
文献类型：
--
作者：
Hudson JS;Ding L;Le V;Lewis E;Graves D
蛋白质对G-四链体结构的特异性识别为体内G-四链体结构的功能作用提供了证据。如前所述，核糖核蛋白hnRNPA 1是蛋白水解衍生物，解旋蛋白1（UP 1），与人端粒重复序列d（TTAGGG）n形成的G-四链体结构结合并使其不稳定。UP 1被认为参与了端粒酶向端粒的募集以进行链延伸。在这项研究中，详细的热力学特性的结合UP 1的人类端粒重复序列，d[AGGG（TTAGGG）3] G-四链体，提出并揭示了关键的见解UP 1诱导的展开的G-四链体结构。UP 1-G-quadruplex的相互作用被证明是由热力学驱动的，在Na+和K+ G-quadruplex-UP 1复合物的形成过程中表现出很大的负焓变（ΔH值分别为−43和−19 kcal/mol）。这些数据揭示了三个不同的双链贡献的相互作用的UP 1与Na+形式的G-四链体DNA。初始相互作用的特征在于结合亲和力为8.5 × 108 M-1（链），比UP 1与具有可比但非四链体形成序列的单链DNA的结合强200倍[4.1 × 106 M-1（链）]。圆二色性光谱揭示了G-四链体的Na+形式被UP 1以2：1的结合比（UP 1：G-四链体DNA）完全展开。这里提出的数据表明，有利的能量的初始结合事件密切耦合，并驱动G-四链体结构的展开。
The specific recognition by proteins of G-quadruplex structures provides evidence of a functional role for in vivo G-quadruplex structures. As previously reported, the ribonucleoprotein, hnRNP Al, and it is proteolytic derivative, unwinding protein 1 (UP1), bind to and destabilize G-quadruplex structures formed by the human telomeric repeat d(TTAGGG)n. UP1 has been proposed to be involved in the recruitment of telomerase to telomeres for chain extension. In this study, a detailed thermodynamic characterization of the binding of UP1 to a human telomeric repeat sequence, the d[AGGG(TTAGGG)3] G-quadruplex, is presented and reveals key insights into the UP1-induced unfolding of the G-quadruplex structure. The UP1–G-quadruplex interactions are shown to be enthalpically driven, exhibiting large negative enthalpy changes for the formation of both the Na+ and K+ G-quadruplex–UP1 complexes (ΔH values of −43 and −19 kcal/mol, respectively). These data reveal three distinct enthalpic contributions from the interactions of UP1 with the Na+ form of G-quadruplex DNA. The initial interaction is characterized by a binding affinity of 8.5 × 108 M–1 (strand), 200 times stronger than the binding of UP1 to a single-stranded DNA with a comparable but non-quadruplex-forming sequence [4.1 × 106 M–1 (strand)]. Circular dichroism spectroscopy reveals the Na+ form of the G-quadruplex to be completely unfolded by UP1 at a binding ratio of 2:1 (UP1:G-quadruplex DNA). The data presented here demonstrate that the favorable energetics of the initial binding event are closely coupled with and drive the unfolding of the G-quadruplex structure.
登录
查看更多内容
影响因子：
2.1
作者：
Fukuda, H;Katahira, M;Nakagama, H
通讯作者：
Nakagama, H
影响因子：
2.9
作者：
Antonacci, Cosimo;Chaires, Jonathan B.;Sheardy, Richard D.
通讯作者：
Sheardy, Richard D.
影响因子：
2.9
作者：
Le VH;Buscaglia R;Chaires JB;Lewis EA
通讯作者：
Lewis EA
影响因子：
14.9
作者：
Lane AN;Chaires JB;Gray RD;Trent JO
通讯作者：
Trent JO
影响因子：
11.4
作者：
MAYEDA, A;MUNROE, SH;KRAINER, AR
通讯作者：
KRAINER, AR