A thymine tetrad in d(TGGGGT) quadruplexes stabilized with Tl+/Na+ ions

A thymine tetrad in d(TGGGGT) quadruplexes stabilized with Tl+/Na+ ions
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DOI:
10.1093/nar/gkh269
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发表时间:
2004-02-01
影响因子:
14.9
通讯作者:
Subirana, JA
Subirana, JA
中科院分区:
生物学2区
文献类型:
--
作者:
Cáceres, C;Wright, G;Subirana, JA

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本文报道了四链体d(TGGGGT)(4)的两种新结构。在其中一个端粒中发现了胸腺嘧啶四联体,因此酵母端粒序列d(TG(1-3))可能形成了同时包含鸟嘌呤和胸腺嘧啶四联体的连续四链体结构。我们的研究还显示,与之前的研究相比,胸腺嘧啶的排列存在显着差异。我们发现五种不同类型的组织:(i)与相邻四链体的鸟嘌呤氢键结合的沟槽;(ii)部分有序的沟槽结合,没有任何氢键;(iii)堆叠的胸腺嘧啶三联体,形成在四链体的3'端;(iv)两个鸟嘌呤四联体之间的胸腺嘧啶四联体。胸腺嘧啶通过单个氢键成对稳定。中心钠离子与两个胸腺嘧啶相互作用,并有助于四分体结构。(v)完全无序的胸腺嘧啶,在晶体中没有显示任何清晰的位置。四分体被Na+或Tl+离子稳定。我们表明,通过使用MAD方法,Tl+可以明确地定位和区分Na+。因此,我们可以确定在我们使用的条件下,在结构的每个离子位点中对任一离子的偏好。
We report two new structures of the quadruplex d(TGGGGT)(4) obtained by single crystal X-ray diffraction. In one of them a thymine tetrad is found. Thus the yeast telomere sequences d(TG(1-3)) might be able to form continuous quadruplex structures, involving both guanine and thymine tetrads. Our study also shows substantial differences in the arrangement of thymines when compared with previous studies. We find five different types of organization: (i) groove binding with hydrogen bonds to guanines from a neighbour quadruplex; (ii) partially ordered groove binding, without any hydrogen bond; (iii) stacked thymine triads, formed at the 3' ends of the quadruplexes; (iv) a thymine tetrad between two guanine tetrads. Thymines are stabilized in pairs by single hydrogen bonds. A central sodium ion interacts with two thymines and contributes to the tetrad structure. (v) Completely disordered thymines which do not show any clear location in the crystal. The tetrads are stabilized by either Na+ or Tl+ ions. We show that by using MAD methods, Tl+ can be unambiguously located and distinguished from Na+. We can thus determine the preference for either ion in each ionic site of the structure under the conditions used by us.