Dynamical Studies of Functionally Altered Mutants of the Tryptophan Repressor Protein
色氨酸阻遏蛋白功能改变突变体的动力学研究
基本信息
- 批准号:0444056
- 负责人:
- 金额:$ 40.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-07-01 至 2009-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The long-term goal of this project is to provide a better understanding of the interconnections between internal dynamics, protein structures, and functions. The internal dynamics of backbone and sidechain atoms of wild-type and functionally altered mutants of the 25 kDa tryptophan repressor (TrpR) protein will be studied using NMR relaxation approaches. TrpR is part of a large family of bacterial proteins that regulate the expression of metabolic genes by binding to DNA operator sequences in response to cellular needs. The repressor's affinity for DNA is controlled by L-tryptophan (L-trp), an allosteric effector that activates the TrpR. The intrinsic flexibility of the TrpR protein structure is thought to be at the origin of the non-cooperativity of binding of the L-tryptophan corepressor to TrpR, and of the non-local long-range effects observed in a temperature-sensitive mutant of the tryptophan repressor protein, L75F-TrpR, which cannot be simply explained by small structural changes when compared to the wild-type TrpR. A second TrpR mutant of interest is A77V which, like L75F, is structurally similar to wild type TrpR and possesses biophysical features analogous to those of L75F-TrpR. Despite similar structures and biophysical features, the two TrpR mutants yield very distinct phenotypes and have very different L-trp cofactor binding properties. Such biochemical differences cannot be explained by the presence of distinct structural changes. The hypothesis to be examined with the NMR relaxation experiments is that the source of the differential L-trp binding properties of the A77V and L775F TrpR proteins originate from differences in intrinsic flexibility and molecular mobility which cannot be identified from inspection of the protein structures. The objective of this project is to provide new insights into the biochemical role of internal motions in modulating TrpR-L-trp-cofactor complex formation and TrpR-DNA recognition. This research will train graduate and undergraduate students in cross-disciplinary research involving NMR-based structural biology and fundamentals of protein chemistry. In addition, the PI will use knowledge obtained from this research to develop a graduate level course in biophysics focusing on the thermodynamics of ligand binding, protein-protein and protein-nucleic acid interactions, role of structural stability and dynamics in modulating protein functions, and allosteric regulations of multivalent protein systems.
该项目的长期目标是更好地了解内部动力学,蛋白质结构和功能之间的相互联系。 将使用NMR弛豫方法研究25 kDa色氨酸阻遏物(TrpR)蛋白的野生型和功能改变的突变体的骨架和侧链原子的内部动力学。TrpR是细菌蛋白质大家族的一部分,其通过结合DNA操纵子序列来调节代谢基因的表达以响应细胞需要。阻遏物对DNA的亲和力由L-色氨酸(L-trp)控制,L-trp是一种激活TrpR的变构效应物。TrpR蛋白质结构的内在灵活性被认为是L-色氨酸辅阻遏物与TrpR结合的非协同性的起源,以及在色氨酸阻遏蛋白L75 F-TrpR的温度敏感突变体中观察到的非局部长程效应的起源,当与野生型TrpR相比时,这不能简单地用小的结构变化来解释。第二种感兴趣的TrpR突变体是A77 V,其与L75 F一样,在结构上类似于野生型TrpR,并且具有类似于L75 F-TrpR的生物物理特征。尽管相似的结构和生物物理特征,两个TrpR突变体产生非常不同的表型,并具有非常不同的L-Trp辅因子结合特性。这种生物化学差异不能用不同的结构变化来解释。用NMR弛豫实验检验的假设是,A77 V和L775 F TrpR蛋白质的不同L-trp结合特性的来源源于内在柔性和分子流动性的差异,这不能从蛋白质结构的检查中识别。本项目的目的是提供新的见解的生化作用的内部运动在调制TrpR-L-色氨酸-辅因子复合物的形成和TrpR-DNA识别。这项研究将培养研究生和本科生的跨学科研究,涉及基于核磁共振的结构生物学和蛋白质化学的基础。此外,PI将利用从这项研究中获得的知识开发生物物理学研究生课程,重点是配体结合,蛋白质-蛋白质和蛋白质-核酸相互作用的热力学,结构稳定性和动力学在调节蛋白质功能中的作用,以及多价蛋白质系统的变构调节。
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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Valerie Copie其他文献
Dynamical Studies Of A Temperature-Sensitive Mutant Of The Tryptophan Repressor Protein, L75F-TrpR
- DOI:
10.1016/j.bpj.2008.12.1618 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Valerie Copie;Brian Tripet;Anupam Goel;Lucas Nerbert;Jannette Carey - 通讯作者:
Jannette Carey
Valerie Copie的其他文献
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{{ truncateString('Valerie Copie', 18)}}的其他基金
MRI: Track 3: Acquisition of a Helium Recovery System to Reduce the Consumption of Helium of Montana State University's NMR Core Facility
MRI:轨道 3:采购氦气回收系统以减少蒙大拿州立大学 NMR 核心设施的氦气消耗
- 批准号:
2320009 - 财政年份:2023
- 资助金额:
$ 40.46万 - 项目类别:
Standard Grant
Microbial Dark Matter: Forging New Discoveries in Metabolism
微生物暗物质:新陈代谢的新发现
- 批准号:
1714556 - 财政年份:2017
- 资助金额:
$ 40.46万 - 项目类别:
Standard Grant
MRI: Acquisition of a cryoprobe- and autosampler-equipped AVANCE III 500 MHz solution NMR
MRI:采集配备冷冻探头和自动进样器的 AVANCE III 500 MHz 解决方案 NMR
- 批准号:
1532078 - 财政年份:2015
- 资助金额:
$ 40.46万 - 项目类别:
Standard Grant
CAREER: Structure-Function Studies of a Neurotrophin Receptor Isoform with Novel Neural Differentiation Function
职业:具有新型神经分化功能的神经营养蛋白受体亚型的结构功能研究
- 批准号:
9984562 - 财政年份:2000
- 资助金额:
$ 40.46万 - 项目类别:
Standard Grant
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