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ALS和FTD连接GGCC重复序列的寡核苷酸模型采用的两种G-四联体结构Two G-quadruplex structures adopted by oligonucleotide model of ALS and FTD linked GGGGCC repeats |
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| 课程网址: | http://videolectures.net/encals2017_brcic_structures_adopted/ |
| 主讲教师: | Jasna Brčić |
| 开课单位: | 斯洛文尼亚国家化学研究所 |
| 开课时间: | 2017-07-21 |
| 课程语种: | 英语 |
| 中文简介: |  |
| 课程简介: | The most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a large increase in the number of GGGGCC repeats located within the non-coding region of C9orf72 gene. Non-canonical structures adopted by expanded GGGGCC repeats, including G-quadruplexes, have been proposed to be crucial in pathogenesis. G-rich oligonucleotides can form in the presence of K+ or Na+ ions non-canonical four-stranded structures called G-quadruplexes, composed of stacked layers of G-quartets that are formed by four guanine residues connected by Hoogsteen hydrogen bonds. G-quadruplexes are known to be structurally diverse and their folding sensitive to oligonucleotide sequence and experimental conditions. In addition, several G-quadruplex structures often coexist in solution, representing a great challenge for high-resolution structure determination. Oligonucleotide d[(G4C2)3G4], chosen as the shortest model with the ability to fold intra-molecularly, formed two major and several minor G-quadruplex structures. Structural polymorphism was reduced by dG to 8Br-dG substitution and led to stabilization of two structures in d[(G4C2)3GGBrGG]. Interestingly, relative populations of G-quadruplex structures were sensitive to pH and rate of cooling when folding from thermally denatured state in the presence of K+ ions. Two different folding conditions were established that selectively favor formation of mostly one of the structures, thus facilitating their individual structural characterization with NMR. Two G-quadruplex structures are topologically very similar, however, they exhibit unique structures and distinct dynamic properties. |
| 关 键 词: | 肌萎缩侧索硬化症; 额颞痴呆; C9orf72 |
| 课程来源: | 视频讲座网 |
| 数据采集: | 2021-12-25：zkj |
| 最后编审: | 2021-12-25：zkj |
| 阅读次数: | 52 |