Structure, function, and regulation of the bacterial transcription cycle
Structure, function, and regulation of the bacterial transcription cycle
批准号:
10607993
负责人:
Seth A. Darst
金额:
$83.56万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-05-01 至 2026-04-30
关键词:
AntibioticsBacteriaBacterial RNABehaviorBindingBiologyChemicalsCombined Modality TherapyComplexCryoelectron MicroscopyDNADNA-Directed DNA PolymeraseDNA-Directed RNA PolymeraseDevelopmentDissociationElementsEnzymesFrequenciesGene ExpressionGenetic TranscriptionGoalsHoloenzymesMethodsMolecular ConformationMolecular MachinesProkaryotic CellsRNARegulationRifampicin resistanceRifampinSeriesStructureTranscriptTuberculosisVisualizationantimicrobialinhibitorinsightinterestmanmeltingpromoterresistant strainsmall moleculestructural biologythree dimensional structuretranscription termination
中文摘要
项目摘要
转录是基因表达和RNA聚合酶(RNAP)的主要控制点,
从细菌到人类,都是转录的核心酶。我们的长期目标是了解
转录机制及其调控。确定RNAP的三维结构,
其与DNA、RNA和调节因子的复合物是重要的步骤。我们专注于
特征的原核RNAP。
阐明了转录周期的基本要素,起始、延伸和终止
通过研究原核生物。详细了解整个系统的结构和功能
转录周期对于解释基因表达的基本控制和靶向
RNAP与小分子抗生素。此外,一个复杂的,
分子机器使用结合能和化学能来影响构象变化,
周期,以及监管机构如何调节周期,是根本的利益。
转录周期以一系列稳定的复合物(core <$holo <$RPo <$EC)为标志,
通过瞬时中间体相互转化。稳定状态之间的转换是
由于缺乏结构性信息,人们对繁重的监管知之甚少。重大转变
包括以下步骤:
全酶+启动子DNA è开放启动子复合物(起始)
开放启动子复合体è延伸复合体(启动子逃逸,s解离)
延伸复合物<$core RNAP + DNA +完成的RNA转录物(终止)
每一个过渡的特点是不稳定的,短暂的中间体,
结构生物学的挑战。冷冻电子显微镜(cryo-EM)已成为一种强大的
方法来可视化这些瞬态。我们将冷冻电镜与其他方法相结合,
机械和结构表征瞬态中间体,其控制
细菌转录周期,包括启动子解链、起始至延伸转变,以及
转录终止这些发现将有助于深入了解大分子的行为,
生物学中的机器
英文摘要
Project Summary
Transcription is the major control point of gene expression and RNA polymerase (RNAP), conserved
from bacteria to man, is the central enzyme of transcription. Our long term goal is to understand the
mechanism of transcription and its regulation. Determining three-dimensional structures of RNAP and
its complexes with DNA, RNA, and regulatory factors, is an essential step. We focus on highly
characterized prokaryotic RNAPs.
The basic elements of the transcription cycle, initiation, elongation, and termination, were elucidated
through study of prokaryotes. A detailed structural and functional understanding of the entire
transcription cycle is essential to explain the fundamental control of gene expression and to target
RNAP with small-molecule antibiotics. Moreover, a complete understanding of how a complex,
molecular machine uses binding and chemical energy to effect conformational changes that drive the
cycle, and how regulators modulate the cycle, is of fundamental interest.
The transcription cycle is marked by a series of stable complexes (core è holo è RPo è EC) that
interconvert through transient intermediates. The transitions between stable states are points of
heavy regulation that are poorly understood due to the lack of structural information. Major transitions
include:
Holoenzyme + promoter DNA è open promoter complex (initiation)
Open promoter complex è elongation complex (promoter escape, s dissociation)
Elongation complex è core RNAP + DNA + completed RNA transcript (termination)
Each of these transitions is characterized by unstable, transient intermediates that are extremely
challenging for structural biology. Cryo-electron microscopy (cryo-EM) has emerged as a powerful
method to visualize these transient states. We are combining cryo-EM with other approaches to
mechanistically and structurally characterize transient intermediates that govern transitions in the
bacterial transcription cycle, including promoter melting, the initiation to elongation transition, and
transcription termination. These findings will provide insight into the behavior of macromolecular
machines throughout biology.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Structure, function, and regulation of the bacterial transcription cycle
-
批准号:10394344
-
项目类别:
-
资助金额:$83.56万
-
财政年份:2016
-
负责人:Seth A. Darst
-
依托单位:
Structure, function, and regulation of the bacterial transcription cycle
-
批准号:10388954
-
项目类别:
-
资助金额:$5.36万
-
财政年份:2016
-
负责人:Seth A. Darst
-
依托单位:
Structure, function, and regulation of the bacterial transcription cycle
-
批准号:9921406
-
项目类别:
-
资助金额:$81.12万
-
财政年份:2016
-
负责人:Seth A. Darst
-
依托单位:
Structure, function, and regulation of the bacterial transcription cycle
-
批准号:9071516
-
项目类别:
-
资助金额:$79.1万
-
财政年份:2016
-
负责人:Seth A. Darst
-
依托单位:
Structure, function, and regulation of the bacterial transcription cycle
-
批准号:9271202
-
项目类别:
-
资助金额:$81.12万
-
财政年份:2016
-
负责人:Seth A. Darst
-
依托单位:
Structural studies of RNA polymerase regulation by RNA
-
批准号:8238020
-
项目类别:
-
资助金额:$34.02万
-
财政年份:2012
-
负责人:Seth A. Darst
-
依托单位:
Structural studies of RNA polymerase regulation by RNA
-
批准号:8431355
-
项目类别:
-
资助金额:$31.83万
-
财政年份:2012
-
负责人:Seth A. Darst
-
依托单位:
Structural studies of RNA polymerase regulation by RNA
-
批准号:8794441
-
项目类别:
-
资助金额:$32.98万
-
财政年份:2012
-
负责人:Seth A. Darst
-
依托单位:
Structural studies of RNA polymerase regulation by RNA
-
批准号:8608542
-
项目类别:
-
资助金额:$32.98万
-
财政年份:2012
-
负责人:Seth A. Darst
-
依托单位:
?/ANTI-? COMPLEXES: STAPHYLOCOCCAL AUREUS PHAGE G1 ORF67
-
批准号:8169306
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
STRUCTURAL STUDIES OF BACTERIAL SIGNALLING: SPORULATION CONTROL
-
批准号:8169240
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
A GENERIC METHOD TO STUDY BACTERIOPHAGE/HOST INTERACTIONS
-
批准号:8169128
-
项目类别:
-
资助金额:$0.12万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
STRUCTURAL BASIS FOR MICROTUBULE CROSSLINKING BY THE MAP65 PROTEIN FAMILY
-
批准号:8169310
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
Bacterial RNAP sigma factor structure and function
-
批准号:8055634
-
项目类别:
-
资助金额:$2.26万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
CRYSTAL STRUCTURES OF THE GLYCOPEPTIDE SULFOTRANSFERASE TEG12
-
批准号:8169309
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
STRUCTURE OF A PAUSED TRANSCRIPTION ELONGATION COMPLEX
-
批准号:8169308
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
BACTERIAL RNA POLYMERASE ? FACTOR INTERACTIONS WITH THE PROMOTER -10 ELEMENT
-
批准号:8169305
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
DETERMINE THE STRUCTURAL BASIS FOR ?N INTERACTIONS WITH ITS PROMOTER DNA
-
批准号:8169307
-
项目类别:
-
资助金额:$0.2万
-
财政年份:2010
-
负责人:Seth A. Darst
-
依托单位:
A GENERIC METHOD TO STUDY BACTERIOPHAGE/HOST INTERACTIONS
-
批准号:7954085
-
项目类别:
-
资助金额:$0.59万
-
财政年份:2009
-
负责人:Seth A. Darst
-
依托单位:
STRUCTURAL STUDIES OF BACTERIAL SIGNALLING: SPORULATION CONTROL
-
批准号:7955130
-
项目类别:
-
资助金额:$2.5万
-
财政年份:2009
-
负责人:Seth A. Darst
-
依托单位:
国内基金
海外基金
Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
-
批准号:81971557
-
项目类别:面上项目
-
资助金额:65.0万元
-
批准年份:2019
-
负责人:毛开睿
-
依托单位:
电缆细菌(Cable bacteria)对水体沉积物有机污染的响应与调控机制
-
批准号:51678163
-
项目类别:面上项目
-
资助金额:64.0万元
-
批准年份:2016
-
负责人:许玫英
-
依托单位: