来自人类端粒DNA的平行四重复的晶体结构
Gary N Parkinson1, Michael P H Lee, Stephen Neidle
1The Cancer Research UK Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Nature
|June 7, 2002
概括
人类端粒DNA四重复的晶体结构揭示了独特的平行链排列和循环配置. 这一发现提供了对端粒折叠和蛋白质相互作用的见解,这对于癌症治疗的发展至关重要.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 端粒通过使用富含关氨酸的DNA重复来保护染色体末端.
- 端粒功能障碍与细胞死亡和癌症有关,呈现治疗点.
- 端粒DNA可以形成四链四重复结构.
研究的目的:
- 在生理 (K+) 度下确定人类端粒DNA四重复的晶体结构.
- 为了将这种结构与之前确定的含 (Na+) 四重复结构进行比较.
- 阐明观察到的四重复结构的折叠和潜在的功能影响.
主要方法:
- 结晶学被用来确定四重复的结构.
- 四重复的DNA是由连续四次人类端粒重复形成的.
- 增长条件模仿了细胞内K+度.
主要成果:
- 晶体结构揭示了一个具有独特折叠的平行链四重体.
- 在四重复结构中观察到 (K+) 离子.
- 连接三核酸环采用了一种类似螺旋的布置,其中有基间隙.
结论:
- K+ 诱导的四重复结构与 Na+ 诱导的结构有很大的不同.
- 观察到的DNA折叠为端粒结构和动态提供了一个模型.
- 这种结构可以解释与端粒相关的蛋白质的识别和结合.
相关概念视频
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Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
01:07The DNA Helix
Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most viruses. DNA is composed of two strands of nucleotides that wind around each other to form a spring-like structure called a double helix. However, the double helix is not perfectly symmetrical. Instead, there are regularly occurring grooves in the structure. The major groove occurs where the sugar-phosphate backbones are relatively far apart. This space...
02:05DNA as a Genetic Template
Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
01:25Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...