细菌转录抑制剂NrdR - 一种灵活的多因素核酸传感器
Inna Rozman Grinberg1, Ornella Bimaï1, Saher Shahid1
1Department of Biochemistry and Biophysics, Stockholm University, Sweden.
The FEBS journal
|March 3, 2025
概括
作为一种细菌抑制剂的NrdR将DNA与特定的核酸结合起来. 它的灵活结构,由新的晶体和冷电磁结构揭示,适应最佳的促进剂结合,帮助抗菌设计.
科学领域:
- 结构生物学是结构生物学.
- 细菌学 细菌学是一门学科.
- 分子机制的分子机制
背景情况:
- NrdR是一种细菌转录抑制剂,可以调节核酸减少酶的运作.
- 了解NrdR的机制对于开发新型抗菌剂至关重要.
- 大肠杆菌具有三个NrdR调节的操作子:nrdHIEF,nrdDG和nrdAB.
研究的目的:
- 阐明NrdR的DNA结合和转录抑制的结构基础.
- 研究核酸在NrdR的DNA结合亲和力和特异性的作用.
- 确定NrdR在各种核酸结合和DNA结合状态中的高分辨率结构.
主要方法:
- 进行X射线晶体学以确定NrdR核酸复合物的结构.
- 低温电子显微镜 (cryo-EM) 用于可视化与DNA结合的NrdR和NrdR光纤.
- 生物化学测试以评估NrdR与不同DNA位点和核酸组合的结合 afinities.
主要成果:
- 获得了NrdR-ATP-dATP和NrdR-ADP-dATP复合物的第一个高分辨率晶体结构.
- 低温EM揭示了与DNA结合的NrdR和新型NrdR纤维的结构.
- 当与ATP/dATP或二酸相应物结合时,NrdR的结合强度在三个大肠杆菌操作子中是相似的;其他腺因核酸不会促进DNA结合.
- 结构分析显示了NrdR的Zn-Ribbon和ATP-cone领域的灵活性,在DNA结合时出现了显著的形状变化.
- 与ATP结合的NrdR线丝将DNA结合残留物隔离,防止DNA相互作用.
结论:
- NrdR具有显著的结构灵活性,在与特定核酸相互作用时适应其构造以获得最佳的DNA结合.
- 核酸依赖的构造变化对NrdR作为转录抑制剂的功能至关重要.
- 这些发现为设计针对NrdR的抗菌剂提供了结构性基础.
相关概念视频
Bacterial RNA Polymerase
28.4K
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
28.4K
Types of RNA
63.0K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
63.0K
Prokaryotic Transcriptional Activators and Repressors
20.7K
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...
20.7K
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Riboswitches
8.0K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.0K
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K


