蛋白质结合分子开关通过宿主-客稳定DNA针头
D Calvin Harris1, Benjamin R Saks, Janarthanan Jayawickramarajah
1Department of Chemistry, Tulane University, 2015 Percival Stern Hall, New Orleans, Louisiana 70118, USA.
Journal of the American Chemical Society
|May 4, 2011
概括
研究人员开发了一种新的DNA分子开关. 这种开关使用β-cyclodextrin和adamantane相互作用来控制蛋白质结合,使新的响应性生物分子系统成为可能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 合成生物学 合成生物学
背景情况:
- 大自然利用分子开关,通过外部刺激调节蛋白质结合活性.
- 这种响应性系统的 De novo 设计构成了重大的科学挑战.
研究的目的:
- 开发一种基于DNA的新型分子开关.
- 创建一个由寡核酸输入控制蛋白质结合活性的系统.
- 模仿自然响应的分子系统.
主要方法:
- 利用一个分子内β-cyclodextrin (β-CD) /adamantane宿主-客人相互作用.
- 设计一个稳定的DNA发针结构.
- 调查寡核酸 (ODN) 选择性的结构转化,从发针到双重.
主要成果:
- 一个稳定的DNA发针 (ΔT(m) = 17 °C) 被生成.
- 该DNA发针经历了ODN选择性形态切换,从茎环到双环.
- 这种切换将系统从一个不活跃的,封装状态转换为一个活跃的,可访问的蛋白质结合复合体.
结论:
- 开发的战略提供了一种方法来创建新的ODN响应蛋白质结合剂.
- 针头域可以被设计为对各种ODN序列的响应.
- 贝塔-赛克洛德克斯的宿主特性促进了小分子的结合,从而产生蛋白相互作用.
相关概念视频
Single-Strand DNA Binding Proteins
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
DNA Helicases
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...


