Supplement
补充
基本信息
- 批准号:10623041
- 负责人:
- 金额:$ 7.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-15 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:ATP-Binding Cassette TransportersAdenosine TriphosphateAffinityAntibiotic ResistanceAntibioticsAwardBacteriaBindingBinding ProteinsBiochemicalBioinformaticsBiological AssayBiological ModelsBiophysicsCarrier ProteinsCell SurvivalCell membraneCellsClassification SchemeComplexComputer ModelsCore AssemblyCoupledCuesCytoplasmDSPP geneDataDipeptidesDockingElectrophoretic Mobility Shift AssayEnsureEnvironmentEscherichia coliFamilyFundingGatekeepingGenomeGlutathioneGoalsHaemophilus influenzaeHemeHeme IronHydrolysisImmuneIn VitroInflammationLaboratoriesMembraneMolecularNickelNontypable Haemophilus influenzaNucleotidesNutrientOligopeptidesOperonOrganismOtitis MediaParentsPasteurellaceaePeptide TransportPeptidesPlayPrevalenceProductionProteinsRegulationResearchResearch PersonnelRespiratory DiseaseRespiratory SystemRiceRoleSH2D1A geneSeriesSourceSpecificityStarvationSurface Plasmon ResonanceSystemTestingTherapeuticTimeTissuesToxinTransmembrane DomainVirulence FactorsWorkWorld Health Organizationantimicrobial peptidebasecofactorcomparativeexperimental studygene cloninggraduate studentheme aheme-binding proteinhost colonizationin silicoin vivoinsightmiddle earmutantnovelparent grantpathogenpathogenic bacteriaperiplasmprogramsresistance mechanismstructural biologyuptake
项目摘要
I. SUMMARY OF THE FUNDED PARENT AWARD R01 GM140584
This proposal seeks to understand how proteins located in the cell membrane work as gatekeepers to
selectively allow compounds into or out of the cell. Such gatekeepers are known as ATP-binding cassette (ABC)
transporters because they use the energy of ATP (adenosine triphosphate) hydrolysis to transport compounds
across the cell membrane. Bacterial ABC importers are essential for organism survival, controlling the rate of
uptake for nutrients scavenged from the bacterium's environment. Control of the rate of transport precludes over-
accumulation of a nutrient that is beneficial at low concentrations but is potentially toxic at high concentrations.
While a subset of ABC proteins contain an additional “accessory” domain that can regulate the uptake of
compounds by shutting off the transporter, it is unclear why certain transporters contain these domains while
others do not. However, we do understand that certain transporters are “turned off” when a specific compound
or protein binds to this accessory domain. Other accessory domains regulate by “sensing” changes in the
microenvironment and reacting accordingly. To decipher this mechanism of regulation, the PI's laboratory
combines biochemical and biophysical experiments with structural biology to understand how these accessory
domains play a role in transport regulation, which in restricts or allows nutrients to enter the cell. This research
program will define the molecular mechanism that controls nutrient uptake and allow researchers to understand
how multiple transport systems work in concert within an organism to maintain cell survival. We will test our
hypothesis that regulation of transporter activation via a sensing accessory protein. The proposed research will
decipher the complex circuitry of regulation in a model system in three Aims to: (1) understand how PepT SBPs
select for different substrates within the microenvironment (i.e., nutrients, cofactors, and peptides); (2) determine
how the assembly of the core transporter dictates transport selectivity and efficiency (3) reveal how PepT
transporters regulate the import of substrates into the cell through the activation of a novel regulatory domain.
This research program has set out to close critical gaps in the understanding of the fundamentals of the transport
mechanism present in all bacteria. The results will yield insights into how regulatory domains modulate transport
across all organisms, crucial for cell viability.
There are no changes to the funded parent award
一、资助家长奖 R01 GM140584 概要
该提案旨在了解位于细胞膜中的蛋白质如何充当守门人
选择性地允许化合物进入或离开细胞。这种看门人被称为 ATP 结合盒 (ABC)
转运蛋白,因为它们利用 ATP(三磷酸腺苷)水解的能量来转运化合物
穿过细胞膜。细菌 ABC 输入者对于生物体的生存至关重要,控制着细菌的传播速度
吸收从细菌环境中清除的营养物质。控制运输速度可防止过度运输
营养物质的积累,在低浓度下有益,但在高浓度下可能有毒。
虽然 ABC 蛋白的一个子集包含一个额外的“辅助”结构域,可以调节
通过关闭转运蛋白来合成化合物,目前尚不清楚为什么某些转运蛋白含有这些结构域,而
其他人则不然。然而,我们确实知道,当特定化合物出现时,某些转运蛋白会被“关闭”
或蛋白质结合到该辅助结构域。其他辅助域通过“感知”变化来调节
微环境并做出相应的反应。为了破译这种调节机制,PI 的实验室
将生物化学和生物物理实验与结构生物学相结合,以了解这些附件如何
结构域在运输调节中发挥作用,限制或允许营养物质进入细胞。这项研究
该计划将定义控制营养吸收的分子机制,并让研究人员了解
多个运输系统如何在生物体内协同工作以维持细胞存活。我们将测试我们的
通过传感辅助蛋白调节转运蛋白激活的假设。拟议的研究将
破译模型系统中复杂的调节电路,旨在实现以下三个目的:(1) 了解 PepT SBP 是如何工作的
选择微环境中的不同底物(即营养素、辅因子和肽); (2)确定
核心转运蛋白的组装如何决定转运选择性和效率 (3) 揭示 PepT 如何发挥作用
转运蛋白通过激活新的调节域来调节底物进入细胞的过程。
该研究计划旨在弥合对交通基础知识理解的关键差距
机制存在于所有细菌中。结果将深入了解监管领域如何调节运输
在所有生物体中,对于细胞活力至关重要。
资助的家长奖励没有变化
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Heather Wendy Pinkett其他文献
Heather Wendy Pinkett的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Heather Wendy Pinkett', 18)}}的其他基金
Molecular Biophysics Training Program at Northwestern University
西北大学分子生物物理学培训项目
- 批准号:
10405487 - 财政年份:2021
- 资助金额:
$ 7.85万 - 项目类别:
Molecular Biophysics Training Program at Northwestern University
西北大学分子生物物理学培训项目
- 批准号:
10615114 - 财政年份:2021
- 资助金额:
$ 7.85万 - 项目类别:
A novel multifunctional role of diverse substrate binding and import by the Haemophilus Sap transporter
嗜血杆菌汁液转运蛋白多种底物结合和输入的新型多功能作用
- 批准号:
10582420 - 财政年份:2020
- 资助金额:
$ 7.85万 - 项目类别:
相似海外基金
Adenosine triphosphate as a master variable for biomass in the oceanographic context
三磷酸腺苷作为海洋学背景下生物量的主变量
- 批准号:
2319114 - 财政年份:2023
- 资助金额:
$ 7.85万 - 项目类别:
Standard Grant
Characterizing the Interaction Between Adenosine Triphosphate and Pathological Alpha-synuclein Structures in Parkinson's Disease
表征帕金森病中三磷酸腺苷与病理性 α-突触核蛋白结构之间的相互作用
- 批准号:
565727-2021 - 财政年份:2021
- 资助金额:
$ 7.85万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Investigation of the development of pain during orthodontic tooth movement with adenosine triphosphate
三磷酸腺苷正畸牙齿移动过程中疼痛发生的研究
- 批准号:
20K18789 - 财政年份:2020
- 资助金额:
$ 7.85万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Neural Regulation of Adenosine Triphosphate (ATP) in the Nasal Mucosa
鼻粘膜三磷酸腺苷 (ATP) 的神经调节
- 批准号:
19K18793 - 财政年份:2019
- 资助金额:
$ 7.85万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
- 批准号:
460605-2014 - 财政年份:2016
- 资助金额:
$ 7.85万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Development of an Analytical Tool Utilizing Electrochemical Detection Methods For the Measuring of Protein Kinase Activity on a Protein Substrate Using Ferrocene-Adenosine Triphosphate (Fc-ATP) as a C
利用电化学检测方法开发分析工具,以二茂铁-三磷酸腺苷 (Fc-ATP) 作为 C,测量蛋白质底物上的蛋白激酶活性
- 批准号:
469948-2014 - 财政年份:2016
- 资助金额:
$ 7.85万 - 项目类别:
Vanier Canada Graduate Scholarship Tri-Council - Doctoral 3 years
Adenosine Triphosphate as a Signal for Evaluating Microbial Risk from Groundwater Supplies
三磷酸腺苷作为评估地下水供应微生物风险的信号
- 批准号:
507411-2016 - 财政年份:2016
- 资助金额:
$ 7.85万 - 项目类别:
Engage Grants Program
Development of an Analytical Tool Utilizing Electrochemical Detection Methods For the Measuring of Protein Kinase Activity on a Protein Substrate Using Ferrocene-Adenosine Triphosphate (Fc-ATP) as a C
利用电化学检测方法开发分析工具,以二茂铁-三磷酸腺苷 (Fc-ATP) 作为 C,测量蛋白质底物上的蛋白激酶活性
- 批准号:
469948-2014 - 财政年份:2015
- 资助金额:
$ 7.85万 - 项目类别:
Vanier Canada Graduate Scholarship Tri-Council - Doctoral 3 years
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
- 批准号:
460605-2014 - 财政年份:2015
- 资助金额:
$ 7.85万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
- 批准号:
460605-2014 - 财政年份:2014
- 资助金额:
$ 7.85万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral














{{item.name}}会员




