Membrane Protein Stability
膜蛋白稳定性
基本信息
- 批准号:9178659
- 负责人:
- 金额:$ 33.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2018-11-30
- 项目状态:已结题
- 来源:
- 关键词:AchievementAddressBasic ScienceBindingBiologicalBiophysicsBurialCell physiologyChargeChemicalsComputer SimulationCouplingDataDependenceDiseaseEngineeringEquilibriumEscherichia coliFree EnergyGoalsGrantHeadHuman bodyHydrophobicityKineticsKnowledgeLeadLipidsLocationMeasurementMeasuresMembraneMembrane ProteinsModelingMolecularMolecular ConformationMutationOrganic solvent productPharmaceutical PreparationsPlayPositioning AttributeProcessProtein EngineeringProteinsRegulationResearchRoleScaffolding ProteinSideSiteSorting - Cell MovementSpecific qualifier valueStructural ProteinStructureTestingTherapeuticThermodynamicsWaterWorkaspartylglutamatebasebiophysical analysisbiophysical techniquescombatdesigndriving forceexperimental studyinsightmicrobialmicroorganismmutantnovelprotein foldingprotein misfoldingprotein structurepublic health relevancescaffold
项目摘要
DESCRIPTION (provided by applicant): Membrane proteins play essential roles in many cellular processes. The overall goal of the proposed research is to understand the physical basis of the protein folding process and the biophysical basis of membrane protein structures. At present, neither of these is well understood for membrane proteins. Thermodynamically, our work addresses the critical role that hydrophobicity plays in membrane protein folds. In the previous granting period, we developed a novel hydrophobicity scale that measures side-chain transfer free energies from water to the membrane center using a real bilayer and a real, folded membrane protein. Based on this achievement, we now propose to test the generality of this scale (1) By measuring side-chain transfer free energies using distinct membrane protein scaffolds; (2) By determining how extent-of-burial in the bilayer modulates water to bilayer transfer free energies; and (3) By engineering of our protein scaffold for measurements as a function of pH to address how the energetic consequences of ionizable group mutations vary with charge state. Kinetically, we discovered in the previous grant period that E. coli lipid head
groups may act as energetic potentials that sort membrane proteins away from the wrong (inner) membranes and towards the correct (outer) membrane locations. We propose in a fourth aim to dissect the biophysical basis for this sorting by determining the kinetic lifetimes and conformations and activation energies to folding induced by E. coli-containing lipid head groups.
描述(由申请人提供):膜蛋白在许多细胞过程中起重要作用。本研究的总体目标是了解蛋白质折叠过程的物理基础和膜蛋白结构的生物物理基础。目前,这两种方法对膜蛋白都没有很好的了解。从热力学上讲,我们的工作解决了疏水性在膜蛋白折叠中的关键作用。在之前的授权期内,我们开发了一种新的疏水性量表,使用真正的双分子层和真正的折叠膜蛋白来测量从水到膜中心的侧链转移自由能。基于这一成果,我们现在建议测试该量表的普遍性(1)通过测量使用不同膜蛋白支架的侧链转移自由能;(2)通过确定在双层中的埋藏程度如何调节水向双层传递自由能;(3)通过设计我们的蛋白质支架来测量pH值的函数,以解决可电离基团突变的能量后果如何随电荷状态而变化。动力学上,我们在之前的资助期发现大肠杆菌脂质头部
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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Karen G. Fleming其他文献
A team of chaperones play to win in the bacterial periplasm
一组伴侣蛋白力争在细菌周质中发挥作用 。
- DOI:
10.1016/j.tibs.2024.03.015 - 发表时间:
2024-08-01 - 期刊:
- 影响因子:11.000
- 作者:
Taylor Devlin;Karen G. Fleming - 通讯作者:
Karen G. Fleming
Energetics of Dimeric FkpA Binding to a Native Unfolded Membrane Protein Client
- DOI:
10.1016/j.bpj.2019.11.2101 - 发表时间:
2020-02-07 - 期刊:
- 影响因子:
- 作者:
Michaela A. Roskopf;Dagan C. Marx;Karen G. Fleming - 通讯作者:
Karen G. Fleming
Towards Understanding How Water Modulates Membrane Protein Stability
- DOI:
10.1016/j.bpj.2019.11.325 - 发表时间:
2020-02-07 - 期刊:
- 影响因子:
- 作者:
Dagan C. Marx;Karen G. Fleming - 通讯作者:
Karen G. Fleming
FkpA enhances outer membrane protein folding using an extensive interaction interface
- DOI:
10.1016/j.bpj.2023.11.1353 - 发表时间:
2024-02-08 - 期刊:
- 影响因子:
- 作者:
Taylor A. Devlin;Dagan C. Marx;Anneliese Faustino;Michaela Roskopf;Stephen D. Fried;Karen G. Fleming - 通讯作者:
Karen G. Fleming
Measuring The Energetic Cost Of Burying An Arginine Sidechain Into A Lipid Bilayer Using A Transmembrane Protein
- DOI:
10.1016/j.bpj.2008.12.1766 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Preston Moon;Karen G. Fleming - 通讯作者:
Karen G. Fleming
Karen G. Fleming的其他文献
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{{ truncateString('Karen G. Fleming', 18)}}的其他基金
2010 Biomolecular Interactions & Methods GRC & GRS
2010 生物分子相互作用
- 批准号:
7800232 - 财政年份:2009
- 资助金额:
$ 33.96万 - 项目类别:
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