Structure-function properties in liquid organelles
液体细胞器的结构功能特性
基本信息
- 批准号:10396101
- 负责人:
- 金额:$ 31.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AdoptedArchitectureBehaviorBindingBiochemicalBiogenesisBiologicalBiological ModelsCell NucleolusCell physiologyCellular StructuresCharacteristicsChargeClientComplementCryoelectron MicroscopyDataDiseaseElectrostaticsEntropyEvolutionIn VitroInterventionLeadLearningLengthLinkLiquid substanceLiteratureMalignant NeoplasmsMethodsMicroscopicModelingMolecularMolecular ProbesMolecular StructureNeurodegenerative DisordersNuclearOrganellesPhasePhysical condensationPolymersProceduresProcessPropertyProteinsRNA-Protein InteractionResearchRibosomal RNARibosomesRoentgen RaysSiteStructural ModelsStructureStructure-Activity RelationshipSystemTechniquesTheoretical modelTherapeuticWorkbasedesigndriving forceenthalpyexperimental studyin vivokinetic theorymolecular assembly/self assemblyrecruitsegregationstructural biologytheoriestool
项目摘要
Project Abstract
Biomolecular condensates are emerging as central to cellular functions in a wide variety of con-
texts. These condensates often have liquid properties and are assembled from multivalent, polymer-like
molecules. Together, these observations suggest a disordered network of interactions stabilizing the
condensate. Liquid systems are inherently disordered, which would seem to preclude the level of order
necessary for structure-function properties to emerge. However, preliminary results have shown that,
hidden within the liquid disorder, is a hierarchy of molecular assemblies that give structure to the uid.
Furthermore, this structure within the contacts stabilizing the liquid confers crucial functional features
to the condensates. This means that in order to understand how these condensates function, it is
necessary to identify structure in disordered systems. This poses a challenge to the eld of structural
biology because this hierarchical structure cannot be resolved by workhorse techniques like X-ray, NMR,
and cryo-EM. The proposed research will establish methods to identify and characterize structure within
liquid condensates. These methods are based on theoretical modeling using an iterative re nement
procedure analogous to structure determination by NMR. This will be done in two systems that are each
featured in a speci c aim. The rst system is a model system for phase separation that removes com-
plications with identifying and quantifying interaction sites. In determining the microscopic structure
of this \sticker and spacer" binding system, which is thought to be a common motif in liquid conden-
sates, this aim will establish basic principles of how molecular structure can dictate spatial organization
on lengthscales ranging from the recruitment molecular clients to organelle segregation/colocalization.
The second aim will develop the structural modeling techniques on the nucleolus. This nuclear organelle
serves as the assembly site for ribosomes. The proposed research will use in vitro phase separation data
to understand the primary molecular interactions within the granular component (GC) where rRNAs
and protein assemble into ribosomal subunits. The interactions in the GC are primarily electrostatic,
which is di erent than the sticker and spacer motif that is the focus of Aim 1. Next, these interactions
will be used to build a kinetic theory of ribosome subunit assembly. This model will establish how the
molecular structure of GC components facilitates ribosome assembly. The theories for generated in both
aims will be analytic, meaning that they will allow for a thorough exploration of parameter space and
can be readily applied to other systems.
项目摘要
生物分子凝聚物正在成为细胞功能的核心,在各种各样的条件下,
文本.这些缩合物通常具有液体性质,并且由多价聚合物样聚合物组装而成。
分子。总之,这些观察结果表明,一个无序的相互作用网络稳定了
冷凝物。液体系统本质上是无序的,这似乎排除了有序的水平。
结构-功能特性出现的必要条件。然而,初步结果显示,
隐藏在液体无序中的是为UID提供结构的分子组装的层次结构。
此外,接触件内的这种稳定液体的结构赋予了关键的功能特征
到冷凝物。这意味着,为了了解这些冷凝物的功能,
在无序系统中识别结构是必要的。这对结构领域提出了挑战。
因为这种层次结构不能通过X射线,核磁共振,
和冷冻电镜拟议的研究将建立方法来识别和表征结构内
液体冷凝物。这些方法是基于理论建模,使用迭代函数
类似于通过NMR进行结构测定的方法。这将在两个系统中完成,每个系统
在一个特定的目标。rst系统是一种用于相分离的模型系统,
识别和量化相互作用位点的复杂性。在确定显微结构时
这种“贴纸和间隔物”结合系统被认为是液体冷凝器中的常见基序,
这个目标将建立分子结构如何决定空间组织的基本原则
在长度尺度上,从招募分子客户到细胞器分离/共定位。
第二个目标是发展核仁的结构建模技术。这个核细胞器
作为核糖体的装配点。拟议的研究将使用体外相分离数据
了解颗粒组分(GC)中的主要分子相互作用,
和蛋白质组装成核糖体亚基。GC中的相互作用主要是静电作用,
其不同于作为目标1的焦点的贴纸和间隔基序。接下来,这些互动
将用于建立核糖体亚基组装的动力学理论。该模型将确定
GC组分的分子结构促进核糖体组装。两种理论都产生了
目标将是分析性的,这意味着它们将允许彻底探索参数空间,
可以很容易地应用于其他系统。
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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Jeremy David Schmit其他文献
Jeremy David Schmit的其他文献
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{{ truncateString('Jeremy David Schmit', 18)}}的其他基金
Structure-function properties in liquid organelles
液体细胞器的结构-功能特性
- 批准号:
10182774 - 财政年份:2021
- 资助金额:
$ 31.4万 - 项目类别:
Structure-function properties in liquid organelles
液体细胞器的结构功能特性
- 批准号:
10608100 - 财政年份:2021
- 资助金额:
$ 31.4万 - 项目类别:
Theoretical and computational modeling of amyloid aggregation
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8904684 - 财政年份:2014
- 资助金额:
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Theoretical and computational modeling of amyloid aggregation
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- 批准号:
8761359 - 财政年份:2014
- 资助金额:
$ 31.4万 - 项目类别:
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