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Structure and Function of S-adenosyl-L-methionine Riboswitches

S-腺苷-L-甲硫氨酸核糖开关的结构和功能

基本信息

批准号：
8587486
负责人：
Ailong Ke
金额：
$ 30.63万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8587486
关键词：
Address Animal Model Antibiotics Attention Bacillus anthracis Bacillus subtilis Base Pairing Binding Binding Proteins Biochemical Bioinformatics Boxing Cells Characteristics Chemicals Clostridium Collaborations Collection Communities Coupling Dependency Elements Enterococcus Enterococcus faecalis Equilibrium Essential Genes Evolution Excision Exercise Gene Expression Gene Expression Regulation Genetic Genome Genus Mycobacterium Genus staphylococcus Gram-Positive Bacteria Indium Knowledge Life Ligand Binding Ligands Light Listeria Location Mediating Methionine Methods Molecular Conformation Movement Mutation Nature Nucleotides Pattern Positioning Attribute Property Publications RNA Regulation Regulator Genes Resolution Solutions Specificity Streptococcus Structural Models Structure Subarachnoid Hemorrhage System Temperature Testing Time Transcription Process Translation Process Work analog antibiotic design aptamer conformational conversion design feeding inhibitor/antagonist novel pathogen practical application public health relevance research study small molecule systems research tool

项目摘要

DESCRIPTION (provided by applicant): Riboswitches are regulatory RNAs that recognize specific small molecules, usually key metabolites, and "switch" downstream gene expression on or off at either the transcriptional or translational level. The discovery of these short cis-acting RNA elements has drastically changed our understanding of genetic regulatory mechanisms. Riboswitches are especially prevalent in Gram-positive bacteria, exemplified by Bacillus subtilis as a model organism, but are also found to control essential genes in important pathogens such as Bacillus anthracis, Staphylococcus, Enterococcus, Streptococcus, Listeria, Clostridium, and Mycobacterium. This and other characteristics have attracted increasing attention to riboswitch-mediated regulation. The three distinct classes of S-adenosyl methionine (SAM) riboswitches are the most commonly found riboswitch classes in nature. These RNAs represent three independent evolution solutions to achieve specific SAM recognition. We recently determined the crystal structures of SAM riboswitches from two classes, the E. faecalis SMK box and the B. subtilis S box. These structures shed light into the how SAM is specifically recognized, but did not provide enough evidence to support the large SAM-dependent conformational changes observed in the previous genetic and biochemical studies. To fully understand their structure-functional relationship and conformational dynamics, we propose to: (1) Understand the ligand recognition mechanism in the SMK box riboswitch. (2) Characterize the ligand-free SMK conformation and search for eukaryotic riboswitches. (3) Carry out chemical probing experiments to reveal ligand-induced conformational dynamics in the SMK RNA

描述(申请人提供)：核糖开关是一种调控RNA，它识别特定的小分子，通常是关键的代谢物，并在转录或翻译水平上打开或关闭下游基因的表达。这些短小的顺式作用RNA元件的发现极大地改变了我们对基因调控机制的理解。核糖开关在革兰氏阳性菌中尤其普遍，以枯草芽孢杆菌为例作为模式生物，但也被发现控制重要病原体的必需基因，如炭疽杆菌、葡萄球菌、肠球菌、链球菌、李斯特菌、梭状芽孢杆菌和分枝杆菌。这一特点和其他特征引起了人们对核糖开关介导的调控的越来越多的关注。S-腺苷蛋氨酸核糖开关是自然界中最常见的三类核糖开关。这些RNA代表三种独立的进化解决方案，以实现特定的SAM识别。我们最近测定了粪肠球菌SMK盒和枯草杆菌S盒两类SAM核糖开关的晶体结构。这些结构揭示了SAM是如何被特定识别的，但没有提供足够的证据来支持在以前的遗传和生化研究中观察到的依赖SAM的大型构象变化。为了全面了解它们的结构-功能关系和构象动力学，我们建议：(1)了解SMK盒核糖开关中的配体识别机制。(2)鉴定无配体的SMK构象，寻找真核核糖开关。(3)进行化学探测实验，揭示配体诱导的SMK RNA的构象动力学

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

One platform, five brands: how nature cuts the cost on riboswitches.

一个平台，五个品牌：大自然如何降低核糖开关的成本。

DOI：
10.1016/j.jmb.2013.03.036
发表时间：
2013
期刊：
Journal of molecular biology
影响因子：
5.6
作者：
Grigg,JasonC;Ke,Ailong
通讯作者：
Ke,Ailong

Structures of Large RNAs and RNA-Protein Complexes: Toward Structure Determination of Riboswitches.

大 RNA 和 RNA-蛋白质复合物的结构：核糖开关的结构测定。

DOI：
10.1016/bs.mie.2015.02.009
发表时间：
2015
期刊：
Methods in enzymology
影响因子：
0
作者：
Grigg,JasonC;Ke,Ailong
通讯作者：
Ke,Ailong

Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA unwinding and degradation.

DOI：
10.1038/nsmb.2875
发表时间：
2014-09
期刊：
Nature structural & molecular biology
影响因子：
16.8
作者：
Huo Y;Nam KH;Ding F;Lee H;Wu L;Xiao Y;Farchione MD Jr;Zhou S;Rajashankar K;Kurinov I;Zhang R;Ke A
通讯作者：
Ke A

Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli.