由 LacI 拓学指导的工程性转录因子
Ashley N Hersey1, Valerie E Kay1, Sumin Lee1
1Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, Atlanta, GA, USA.
Cell systems
|August 17, 2023
概括
与乳糖抑制剂 (LacI) 一样,体转录因子 (aTF) 已被设计成具有新的功能. 这个视角详细介绍了修改aTF中的蛋白质-DNA/配体相互作用和表型的设计规则.
科学领域:
- 分子生物学分子生物学
- 生物技术是生物技术.
- 合成生物学 合成生物学
背景情况:
- 体转录因子 (aTF) 在生物过程和生物技术中至关重要.
- 乳糖抑制剂 (LacI) 是一种被广泛使用的aTF,作为所有菌调节的模型.
- aTF是合成生物学,基础研究和蛋白质生产的基础.
研究的目的:
- 通过使用 LacI TF 作为模型,探索全转录因子 (aTF) 的工程替代函数.
- 概述修改蛋白质-DNA和蛋白质-连接体相互作用的设计原则.
- 为了证明这些设计规则对LacI/GalR家族内的其他aTF的推断.
主要方法:
- 利用LacI TF作为设计新型全osteric 函数的主要示例.
- 总结设计规则和启发方法,以实现替代蛋白质-DNA相互作用.
- 总结设计规则和启发方法,以实现替代的蛋白质-连接体相互作用和表型机制.
主要成果:
- 拉基作为一种特殊的模型来理解全沟通.
- 介绍了修改aTF函数的工程策略.
- 设计原则证明了改变蛋白质-DNA和蛋白质-连接体结合特异性的设计原则.
- 该研究提供了一个框架,用于将工程策略推断到相关的aTFs.
结论:
- 拉基TF是一个多功能平台,用于设计新的aTF功能.
- 既定的设计规则和启发式可用于设计其他aTF,特别是LacI/GalR家族中的aTF.
- 这项工作推进了aTFs的工程,用于合成生物学及其他领域的各种应用.
相关概念视频
Inducible Operons: lac Operon
48
The lac operon in Escherichia coli is a model for understanding inducible gene regulation and metabolic flexibility. It integrates local control by lactose and global regulation through catabolite repression, enabling E. coli to preferentially metabolize glucose when available and switch to lactose utilization when glucose is scarce.Structure and Function of the lac OperonThe lac operon contains three structural genes: lacZ (β-galactosidase), lacY (lactose permease), and lacA...
48
Operons
49.2K
Prokaryotes can control gene expression through operons—DNA sequences consisting of regulatory elements and clustered, functionally related protein-coding genes. Operons use a single promoter sequence to initiate transcription of a gene cluster (i.e., a group of structural genes) into a single mRNA molecule. The terminator sequence ends transcription. An operator sequence, located between the promoter and structural genes, prohibits the operon’s transcriptional activity if bound by...
49.2K
Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
Transcription Factors
76.1K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
76.1K
Prokaryotic Transcriptional Activators and Repressors
21.2K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
21.2K
Cooperative Binding of Transcription Regulators
6.5K
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...
6.5K


