NMR structure of a G-quadruplex formed by four d(G4C2) repeats: insights into structural polymorphism.
NMR structure of a G-quadruplex formed by four d(G4C2) repeats: insights into structural polymorphism.
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DOI：
10.1093/nar/gky886
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发表时间：
2018-11-30
影响因子：
14.9
通讯作者：
Plavec J
中科院分区：
文献类型：
--
作者：
Brcic J;Plavec J
肌萎缩侧索硬化症(ALS)和额颞性痴呆(FTD)最常见的遗传原因是位于C9orf72基因非编码区的d(G4C2)n·(G2C4)n重复数大幅增加。在扩展的重复序列中形成的非规范结构，包括G-四链，被认为是驱动重复序列扩展和ALS和FTD的发病机制的因素。寡核苷酸d[(G4C2)3G4]代表d(G4C2)的最短寡核苷酸模式，具有形成单分子G-四链体的能力，除了与K+离子共存于溶液中的几个次要物种外，还形成两个主要的G-四链体结构。在这里，我们使用溶液状态核磁共振来确定d[(G4C2)3G4]采用的一个主要G-四链体物种的高分辨结构。通过在21位用8BR-DG一次取代DG，促进了命名为AQU的G-四链体的结构表征，发现了由四个G-四联体和三个侧向C-C环组成的反平行折叠。G-四链体表现出很高的热稳定性，在弱酸性条件下，在动力学上是有利的。在结构中观察到了一种不同于C-四重奏的不寻常的结构元素。两个C·C碱基对堆积在附近的G-四元组上，参与了对称的N3-氨基和羰基-氨基几何构型与质子化C+·C态之间的动态平衡。
Most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), is a largely increased number of d(G4C2)n•(G2C4)n repeats located in the non-coding region of C9orf72 gene. Non-canonical structures, including G-quadruplexes, formed within expanded repeats have been proposed to drive repeat expansion and pathogenesis of ALS and FTD. Oligonucleotide d[(G4C2)3G4], which represents the shortest oligonucleotide model of d(G4C2) repeats with the ability to form a unimolecular G-quadruplex, forms two major G-quadruplex structures in addition to several minor species which coexist in solution with K+ ions. Herein, we used solution-state NMR to determine the high-resolution structure of one of the major G-quadruplex species adopted by d[(G4C2)3G4]. Structural characterization of the G-quadruplex named AQU was facilitated by a single substitution of dG with 8Br-dG at position 21 and revealed an antiparallel fold composed of four G-quartets and three lateral C–C loops. The G-quadruplex exhibits high thermal stability and is favored kinetically and under slightly acidic conditions. An unusual structural element distinct from a C-quartet is observed in the structure. Two C•C base pairs are stacked on the nearby G-quartet and are involved in a dynamic equilibrium between symmetric N3-amino and carbonyl-amino geometries and protonated C+•C state.
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DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.2
作者：
Ash PE;Bieniek KF;Gendron TF;Caulfield T;Lin WL;Dejesus-Hernandez M;van Blitterswijk MM;Jansen-West K;Paul JW 3rd;Rademakers R;Boylan KB;Dickson DW;Petrucelli L
通讯作者：
Petrucelli L
影响因子：
5.4
作者：
Avino, Anna;Portella, Guillem;Eritja, Ramon
通讯作者：
Eritja, Ramon
DOI：
10.1073/pnas.1308421110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Dodge, James C.;Treleaven, Christopher M.;Shihabuddin, Lamya S.
通讯作者：
Shihabuddin, Lamya S.
C9ORF72和P62的复合物使用精氨酸甲基化来消除自噬的应激颗粒。
影响因子：
16.6
作者：
Chitiprolu M;Jagow C;Tremblay V;Bondy-Chorney E;Paris G;Savard A;Palidwor G;Barry FA;Zinman L;Keith J;Rogaeva E;Robertson J;Lavallée-Adam M;Woulfe J;Couture JF;Côté J;Gibbings D
通讯作者：
Gibbings D