Organization and function of a type II secretion complex
II型分泌复合物的组织和功能
基本信息
- 批准号:8075962
- 负责人:
- 金额:$ 37.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-03-01 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:ATP HydrolysisATP phosphohydrolaseAffinity ChromatographyBindingBinding SitesBiochemicalBiologicalCardiolipinsCell membraneCellsChemicalsCleaved cellComplexCytoplasmic ProteinCytoplasmic TailDimerizationElbowElectron MicroscopyEnzymesExcisionFluorescence MicroscopyGenesInfantLigand BindingLigandsMapsMembraneMembrane ProteinsMolecularMolecular ConformationMolecular GeneticsMultiprotein ComplexesMutagenesisMutateNatureNucleotidesPathway interactionsPhospholipidsPoint MutationPositioning AttributeProcessProteinsSiteSuppressor MutationsSurface Plasmon ResonanceSystemTestingTherapeuticTherapeutic UsesToxinVibrio choleraeVirulenceVirulence FactorsZincantimicrobialcell envelopechemical geneticscrosslinkdesigndimerextracellularin vivoinhibitor/antagonistmembrane activitymonomermouse modelmutantnovelpathogenpolymerizationpreventprotein protein interactionresearch studysecretion processsmall moleculetargeted delivery
项目摘要
Extracellular secretion and targeted delivery by the type II secretion (T2S) system is considered a major virulence mechanism in gram negative pathogens, as many of the proteins secreted via the T2S pathway constitute important virulence factors, including toxins and degradative enzymes. The T2S apparatus is comprised of at least 13 different proteins, EpsC-EpsN and PilD, that assemble into a complex that spans the entire cell envelope of Vibrio cholerae. The dynamic and perhaps transient nature of this complex may be a prerequisite for function as its assembly and disassembly may drive extracellular secretion. The energy required for this process is thought to be generated from ATP hydrolysis by EpsE, a cytoplasmic protein that is associated with the cytoplasmic membrane via interaction with the membrane proteins EpsL. EpsM and EpsF. EpsE's interactions with these components modulate its ATPase activity and promote its localization to distinct sites within the V. cholerae cell envelope.
The experiments described in this proposal are designed to test the hypothesis that specific protein-protein interactions and acidic phospholipids drive T2S in an ATP-dependent process at discrete sites In the cell envelope of V. cho/erae. Specffically, this proposal will i) determine the mechanism by which the enzymatic activity of EpsE is controlled by components of the cytoplasmic membrane including phospholipids. EpsL and EpsF; ii) investigate the ordered assembly of Eps components and determine the mechanism by which EpsD and EpsC drive focal assembly of the T2S complex; iii) map the cleft that forms when EpsM assembles and identify the cellular factor that binds to the cleft.
Resolving the mechanisms of regulated assembly and spatial localization of the T2S system will further our understanding of T2S and may identify ways to manipulate the secretion process for preventative, therapeutic and/or biotechnological use.
II型分泌(T2S)系统的细胞外分泌和靶向递送被认为是革兰氏阴性病原体的主要毒力机制,因为通过T2S途径分泌的许多蛋白质构成重要的毒力因子,包括毒素和降解酶。 T2S 装置由至少 13 种不同的蛋白质(EpsC-EpsN 和 PilD)组成,它们组装成一个跨越霍乱弧菌整个细胞包膜的复合物。这种复合物的动态和可能短暂的性质可能是功能的先决条件,因为它的组装和分解可能驱动细胞外分泌。该过程所需的能量被认为是由 EpsE 水解 ATP 产生的,EpsE 是一种细胞质蛋白,通过与膜蛋白 EpsL 相互作用与细胞质膜相关联。 EpsM 和 EpsF。 EpsE 与这些成分的相互作用调节其 ATP 酶活性并促进其定位到霍乱弧菌细胞包膜内的不同位点。
本提案中描述的实验旨在测试以下假设:特定的蛋白质-蛋白质相互作用和酸性磷脂在 V. cho/erae 细胞包膜中离散位点的 ATP 依赖性过程中驱动 T2S。具体来说,该提案将 i) 确定 EpsE 酶活性受细胞质膜成分(包括磷脂)控制的机制。 EpsL 和 EpsF; ii) 研究 Eps 组件的有序组装,并确定 EpsD 和 EpsC 驱动 T2S 复合体焦点组装的机制; iii) 绘制 EpsM 组装时形成的裂口图,并识别与裂口结合的细胞因子。
解决 T2S 系统的调节组装和空间定位机制将进一步加深我们对 T2S 的理解,并可能确定操纵分泌过程以用于预防、治疗和/或生物技术用途的方法。
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)
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Maria B Sandkvist其他文献
Maria B Sandkvist的其他文献
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{{ truncateString('Maria B Sandkvist', 18)}}的其他基金
Antagonistic relationships among Acinetobacter isolates
不动杆菌分离株之间的拮抗关系
- 批准号:
10604520 - 财政年份:2022
- 资助金额:
$ 37.85万 - 项目类别:
Molecular Mechanisms of Protein Sorting by the Type II Secretion System
II 型分泌系统蛋白质分选的分子机制
- 批准号:
10239182 - 财政年份:2018
- 资助金额:
$ 37.85万 - 项目类别:
Molecular Mechanisms of Protein Sorting by the Type II Secretion System
II 型分泌系统蛋白质分选的分子机制
- 批准号:
9790955 - 财政年份:2018
- 资助金额:
$ 37.85万 - 项目类别:
Molecular Mechanisms of Protein Sorting by the Type II Secretion System
II 型分泌系统蛋白质分选的分子机制
- 批准号:
10471257 - 财政年份:2018
- 资助金额:
$ 37.85万 - 项目类别:
Targeting type II secretion, a common virulence pathway
针对 II 型分泌,一种常见的毒力途径
- 批准号:
7631000 - 财政年份:2009
- 资助金额:
$ 37.85万 - 项目类别:
Targeting type II secretion, a common virulence pathway
针对 II 型分泌,一种常见的毒力途径
- 批准号:
7849911 - 财政年份:2009
- 资助金额:
$ 37.85万 - 项目类别:
Organization and function of a type II secretion complex
II型分泌复合物的组织和功能
- 批准号:
7578398 - 财政年份:2002
- 资助金额:
$ 37.85万 - 项目类别:
Organization and Function of a Type II Secretion Complex
II 型分泌复合物的组织和功能
- 批准号:
6849338 - 财政年份:2002
- 资助金额:
$ 37.85万 - 项目类别:
Organization and Function of a Type II Secretion Complex
II 型分泌复合物的组织和功能
- 批准号:
6621947 - 财政年份:2002
- 资助金额:
$ 37.85万 - 项目类别:
Organization and Function of a Type II Secretion Complex
II 型分泌复合物的组织和功能
- 批准号:
6706891 - 财政年份:2002
- 资助金额:
$ 37.85万 - 项目类别: