Rules for Helix Intiation, Propagation, and Termination

螺旋起始、传播和终止的规则

基本信息

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this research program is to understand the detailed physico-chemical basis for the mechanism of protein stability. The function of proteins requires translation of the information encoded by a linear polypeptide sequence into a specific three-dimensional structure. The relationship between protein function, structure and stability is complex. Small perturbations such as single-site mutations can alter protein function, trafficking, degradation rate or solubility, leading to cellular abnormalities that, in some cases, are lethal. However, proteins also possess a great degree of plasticity and there are large number of amino acid mutations that do not affect the overall structure or function. The knowledge of the relationship between sequence, structure and stability is critical for, not only a deeper understanding of biological systems, but also for the development of approaches that allow rational design of new protein structures and enhanced stabilities of biologically active proteins. This can be used in biotechnology for improving human well-being and health. The present research proposal aims to understand how the amino acid sequence determines the stability and specificity of alpha-helical segments, both in solution and within protein structure, and to identify the universal and specialized determinants for protein stability. The four broad questions to be answered are: (1). What is the mechanism of stabilization of the N-termini of a-helices? (2). What is the contribution of the backbone conformation and hydrogen bonding at the C-terminus to the stability of the a-helix? (3). What is the contribution of the enthalpy of helix-coil transition to the helix propensity scale? (4). What is the contribution of helix-coil transition to the energetics of protein-protein interactions? To answer these questions, experiments, that include site-directed mutagenesis, calorimetry, fluorescence, circular dichroism and NMR spectroscopies, and computational approaches, will be applied to the model proteins ubiquitin, human pancreatic polypeptide, calmodulin and S100P, and short monomeric peptides.
描述(由申请方提供):本研究项目的长期目标是了解蛋白质稳定性机制的详细理化基础。 蛋白质的功能需要将线性多肽序列编码的信息翻译成特定的三维结构。 蛋白质的功能、结构和稳定性之间的关系是复杂的。 小的扰动,如单位点突变,可以改变蛋白质的功能,运输,降解速率或溶解度,导致细胞异常,在某些情况下,是致命的。 然而,蛋白质也具有很大程度的可塑性,并且存在大量不影响整体结构或功能的氨基酸突变。 序列,结构和稳定性之间的关系的知识是至关重要的,不仅对生物系统的更深入的理解,而且对开发的方法,允许合理设计新的蛋白质结构和增强生物活性蛋白质的稳定性。 这可用于生物技术,以改善人类福祉和健康。 本研究的目的是了解氨基酸序列如何决定α-螺旋片段的稳定性和特异性,无论是在溶液中还是在蛋白质结构中,并确定蛋白质稳定性的通用和专门的决定因素。 需要回答的四个主要问题是:(1)。 α-螺旋N-末端的稳定机制是什么?(二)、 主链构象和C末端的氢键对α-螺旋稳定性的贡献是什么?(三)、 螺旋-线团转变的焓对螺旋倾向尺度的贡献是什么?(四)、 螺旋-卷曲转变对蛋白质相互作用的能量学有什么贡献?为了回答这些问题,实验,包括定点诱变,量热法,荧光,圆二色性和NMR光谱,和计算方法,将被应用到模型蛋白泛素,人胰腺多肽,钙调蛋白和S100 P,和短单体肽。

项目成果

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GEORGE I MAKHATADZE其他文献

GEORGE I MAKHATADZE的其他文献

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{{ truncateString('GEORGE I MAKHATADZE', 18)}}的其他基金

Computational and Experimental Studies of the Amyloid Fibril Formation by PAPf39
PAPf39 淀粉样原纤维形成的计算和实验研究
  • 批准号:
    8279567
  • 财政年份:
    2012
  • 资助金额:
    $ 28.63万
  • 项目类别:
Computational and Experimental Studies of the Amyloid Fibril Formation by PAPf39
PAPf39 淀粉样原纤维形成的计算和实验研究
  • 批准号:
    8473884
  • 财政年份:
    2012
  • 资助金额:
    $ 28.63万
  • 项目类别:
Biopolymers 2008 Gordon Research Conference
生物聚合物 2008 年戈登研究会议
  • 批准号:
    7478232
  • 财政年份:
    2008
  • 资助金额:
    $ 28.63万
  • 项目类别:
Role of Helix Formation in Mediating Protein-Protein Interactions
螺旋形成在介导蛋白质-蛋白质相互作用中的作用
  • 批准号:
    7939916
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:
Rules for Helix Intiation, Propagation, and Termination
螺旋起始、传播和终止的规则
  • 批准号:
    7161781
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:
Rules for Helix Intiation, Propagation, and Termination
螺旋起始、传播和终止的规则
  • 批准号:
    7069479
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:
RULES FOR HELIX TERMINATION, THE C CAPPING BOX
螺旋终止规则,C 封盖盒
  • 批准号:
    6386349
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:
Rules for Helix Intiation, Propagation, and Termination
螺旋起始、传播和终止的规则
  • 批准号:
    7514104
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:
RULES FOR HELIX TERMINATION, THE C CAPPING BOX
螺旋终止规则,C 封盖盒
  • 批准号:
    2772711
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:
Rules for Helix Intiation, Propagation, and Termination
螺旋起始、传播和终止的规则
  • 批准号:
    6839977
  • 财政年份:
    1998
  • 资助金额:
    $ 28.63万
  • 项目类别:

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