Electrogenic Reactions during Lactose/proton Symport Catalyzed by LacY

LacY 催化的乳糖/质子共传递过程中的生电反应

基本信息

  • 批准号:
    1129551
  • 负责人:
  • 金额:
    $ 64.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-12-01 至 2014-11-30
  • 项目状态:
    已结题

项目摘要

Intellectual merit. One of the major challenges in the broad field of bioenergetics is to understand how nutrients such as sugars and amino acids cross biological membranes and accumulate inside of cells. It is now understood that most living cells function like batteries. Thus, chemical reactions like respiration or ATP hydrolysis are coupled to the pumping of hydrogen ions or sodium out of cells. In this manner, cells or intracellular organelles like mitochondria create an electrochemical gradient of either hydrogen ions or sodium in which the inside of the cell is electrically negative and low in hydrogen ions or sodium relative to the outside. Given this scenario, there is then a driving force on hydrogen ions or sodium to diffuse back into the cell down their electrochemical gradients. Transport proteins embedded in the membrane like the one described in this proposal utilize the free energy released by this energetically downhill movement to drive translocation and accumulation of a specific nutrient in this case, the sugar lactose and it is known that transport of each lactose molecule across the membrane is accompanied by one hydrogen ion. It is the aim of this research to understand the molecular mechanism of this basic and universal biological process by studying the electrical properties of the lactose permease (LacY), a model for the members of the Major Facilitator Superfamily, a huge group of related membrane transport proteins. The project includes the application of an important new technique to observe the electrical properties of this transporter using newly developed solid-supported membrane electrodes.Broader impacts. Studies on active transport and bioenergetics with LacY as the paradigm have revolutionized the field of membrane transport. From (i) the initial discovery that membrane vesicles are useful as a model system to study transport to (ii) the development of probes for quantifying electrical potentials and hydrogen ion gradients in microscopic systems to (iii) site-directed and Cys-scanning mutagenesis to (iv) purifying LacY to homogeneity in a functional state to (v) obtaining X-ray crystal structures to (vi) engineering the symporter for all manner of biochemical and spectroscopic studies, this laboratory has pioneered developments in the field for over 45 years. Most of the breakthroughs in the history of the research have been widely selected for inclusion in various textbooks, reference books and teaching materials in many languages for both undergraduate and graduate teaching worldwide. The PI will continue to speak to high school and university audiences in order to convey scientific knowledge to young people and stimulate their interest in basic science. Invited lectures in symposia, at universities and multi-disciplinary conferences nationally and internationally will serve as multiple channels to convey this novel information to society in a timely manner.
智力上的优点。生物能量学领域的主要挑战之一是了解糖和氨基酸等营养物质如何穿过生物膜并在细胞内积累。 现在人们已经知道,大多数活细胞的功能就像电池一样。因此,像呼吸或ATP水解这样的化学反应与氢离子或钠离子泵出细胞相耦合。以这种方式,细胞或细胞内细胞器(如线粒体)产生氢离子或钠的电化学梯度,其中细胞内部是电负性的,并且相对于外部氢离子或钠含量低。 在这种情况下,氢离子或钠离子就会受到驱动力,沿着电化学梯度扩散回电池中。嵌入膜中的转运蛋白,如本提案中所述的转运蛋白,利用由这种大力下坡运动释放的自由能来驱动特定营养素(在这种情况下为糖乳糖)的移位和积累,并且已知每个乳糖分子跨膜的转运伴随着一个氢离子。本研究的目的是通过研究乳糖通透酶(LacY)的电特性来了解这种基本和普遍的生物过程的分子机制,乳糖通透酶是主要促进剂超家族成员的模型,主要促进剂超家族是一个巨大的相关膜转运蛋白。 该项目包括应用一项重要的新技术,利用新开发的固体支撑膜电极观察这种转运体的电特性。以LacY为范式的主动转运和生物能量学研究彻底改变了膜转运领域。从(i)最初发现膜囊泡可用作研究转运的模型系统,到(ii)开发用于定量微观系统中的电势和氢离子梯度的探针,到(iii)定点和Cys扫描诱变,到(iv)将LacY纯化至功能状态下的均一性,到(v)获得X射线晶体结构,到(vi)该实验室为各种生物化学和光谱研究设计了同向转运体,45年来一直是该领域的先驱。研究历史上的大多数突破已被广泛选择,以多种语言纳入各种教科书,参考书和教学材料,供全球本科生和研究生教学。PI将继续向高中和大学观众演讲,向年轻人传达科学知识,激发他们对基础科学的兴趣。在国内和国际的研讨会、大学和多学科会议上的特邀讲座将成为及时向社会传达这一新信息的多种渠道。

项目成果

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Ronald Kaback其他文献

Observing Insertase- and Translocase-Assisted Insertion and Folding Pathways of Single Transmembrane Transporters
  • DOI:
    10.1016/j.bpj.2017.11.073
  • 发表时间:
    2018-02-02
  • 期刊:
  • 影响因子:
  • 作者:
    Tetiana Serdiuk;Stefania Mari;Ronald Kaback;Daniel Müller
  • 通讯作者:
    Daniel Müller

Ronald Kaback的其他文献

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{{ truncateString('Ronald Kaback', 18)}}的其他基金

EAGER: Molecular Mechanism of Permeases
EAGER:渗透酶的分子机制
  • 批准号:
    1747705
  • 财政年份:
    2017
  • 资助金额:
    $ 64.3万
  • 项目类别:
    Standard Grant
EAGER: Mechanism of Energy Coupling with a Membrane Symport Protein
EAGER:膜信号蛋白能量耦合机制
  • 批准号:
    1547801
  • 财政年份:
    2015
  • 资助金额:
    $ 64.3万
  • 项目类别:
    Standard Grant
Structure of Cation-Coupled Active Sugar Transporters
阳离子偶联活性糖转运蛋白的结构
  • 批准号:
    0450970
  • 财政年份:
    2005
  • 资助金额:
    $ 64.3万
  • 项目类别:
    Continuing Grant

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