Structural and Functional Characterization of Cyanoglobin

蓝红蛋白的结构和功能表征

基本信息

  • 批准号:
    0349409
  • 负责人:
  • 金额:
    $ 59.46万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-03-01 至 2008-01-31
  • 项目状态:
    已结题

项目摘要

The hemoglobin superfamily of proteins has representatives in all kingdoms of organisms. In vertebrates, hemoglobin and its close relative myoglobin are responsible for the transport and storage of molecular oxygen. The relationship between three-dimensional structure and function in these two highly specialized proteins has been explored extensively and is well understood. In invertebrates, hemoglobins exhibit a broader range of physiological roles reflecting essential aspects of globin fold evolution, oxygen utilization, and heme reactivity. For these proteins, however, the connection between structure and function is incompletely defined and it is not yet possible to anticipate chemical properties on the basis of the amino acid sequences. This lack of knowledge limits the usefulness of genome sequencing data and the interpretation of evolutionary relationships. The goal of the project is to investigate primitive hemoglobins from the non-nitrogen fixing cyanobacteria Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7002. Both are hexacoordinate hemoglobins utilizing two histidines to ligate the iron ion, and both undergo a facile post-translational attachment of the heme group apparently unique to them. Biophysical methods (NMR spectroscopy in vitro and in vivo, optical spectroscopy) and biochemical methods (site-directed mutagenesis, genetic manipulations, phenotypic characterization) will be applied to investigate the role of Synechococcus hemoglobin in vivo; determine the three-dimensional structure of Synechocystis and Synechococcus proteins in solution before and after they have undergone the heme modification; and analyze the molecular determinants of heme coordination and reactivity. Comparison will be made to other invertebrate hemoglobins to develop an atomic level understanding of chemical and biochemical properties.The research component of the project provides training opportunities for graduate and undergraduate students and, through a collaboration focused on cyanobacterial physiology and biochemistry, establishes a mechanism for multidisciplinary interactions between the Chemistry department and the Biochemistry and Molecular Biology department. The project also contains three specific educational components that will enhance further its broader impact. The first is the development of three-dimensional visualization modules for an advanced undergraduate biological chemistry course and the inclusion in this course of research-related hemoglobin topics. This is designed to bring the material to life and encourage chemistry students to pursue careers with a life sciences slant. The second is the development of a short course in communication skills aimed at graduate students. The emphasis will be placed on how to convey sophisticated scientific concepts and issues to a general audience. The third is to continue the organization and increase the frequency of inter-departmental structural biology seminars, for which the speakers are advanced students. These activities are expected to prepare undergraduate, graduate, and post-doctoral students for professional careers in academia, industry, and government.
血红蛋白超家族在所有生物界都有代表。在脊椎动物中,血红蛋白及其近亲肌红蛋白负责分子氧的运输和储存。这两种高度特化的蛋白质的三维结构和功能之间的关系已被广泛探索,并得到很好的理解。在无脊椎动物中,血红蛋白表现出更广泛的生理作用,反映了球蛋白折叠进化,氧利用和血红素反应性的重要方面。然而,对于这些蛋白质,结构和功能之间的联系还没有完全确定,并且还不可能根据氨基酸序列预测化学性质。这种知识的缺乏限制了基因组测序数据的有用性和对进化关系的解释。该项目的目的是研究非固氮蓝藻集胞藻属PCC 6803和集胞藻属PCC 7002的原始血红蛋白。两者都是利用两个组氨酸连接铁离子的六配位血红蛋白,并且两者都经历了血红素组的简单翻译后附着,这显然是它们所独有的。Biophysical methods(体外和体内NMR光谱,光学光谱)和生物化学方法(定点诱变、遗传操作、表型表征)将被应用于研究聚球藻血红蛋白在体内的作用;确定聚胞藻和聚球藻蛋白在它们经历血红素修饰之前和之后在溶液中的三维结构;并分析血红素配位和反应性的分子决定因素。通过与其他无脊椎动物血红蛋白的比较,以发展对化学和生物化学性质的原子水平理解。该项目的研究部分为研究生和本科生提供培训机会,并通过专注于蓝藻生理学和生物化学的合作,建立了化学系与生物化学和分子生物学系之间多学科互动的机制。该项目还包括三个具体的教育组成部分,将进一步加强其更广泛的影响。第一个是三维可视化模块的高级本科生物化学课程的发展,并在这门课程的研究相关的血红蛋白主题的列入。这是为了使材料的生活,并鼓励化学学生追求职业生涯与生命科学的倾斜。第二个是为研究生开设短期交流技能课程。重点将放在如何向一般观众传达复杂的科学概念和问题。第三是继续组织和增加跨部门的结构生物学研讨会的频率,演讲者是高级学生。这些活动预计准备本科生,研究生和博士后学生在学术界,工业界和政府的职业生涯。

项目成果

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Juliette Lecomte其他文献

A Histidine-Lysine Axial Ligand Switch in a Hemoglobin
  • DOI:
    10.1016/j.bpj.2017.11.2246
  • 发表时间:
    2018-02-02
  • 期刊:
  • 影响因子:
  • 作者:
    Dillon Nye;Matthew Preimesberger;Ananya Majumdar;Juliette Lecomte
  • 通讯作者:
    Juliette Lecomte

Juliette Lecomte的其他文献

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{{ truncateString('Juliette Lecomte', 18)}}的其他基金

EAGER: Toward determining the key interactions between the SARS-CoV2 virus components and host cells
EAGER:致力于确定 SARS-CoV2 病毒成分与宿主细胞之间的关键相互作用
  • 批准号:
    2031790
  • 财政年份:
    2020
  • 资助金额:
    $ 59.46万
  • 项目类别:
    Standard Grant
Building quaternary structure in heme proteins
构建血红素蛋白的四级结构
  • 批准号:
    2003950
  • 财政年份:
    2020
  • 资助金额:
    $ 59.46万
  • 项目类别:
    Standard Grant
Structural and dynamic characterization of 2/2 hemoglobins
2/2 血红蛋白的结构和动态表征
  • 批准号:
    1330488
  • 财政年份:
    2013
  • 资助金额:
    $ 59.46万
  • 项目类别:
    Continuing Grant
Structural and Dynamic Characterization of 2/2 Hemoglobins
2/2 血红蛋白的结构和动态表征
  • 批准号:
    0843439
  • 财政年份:
    2009
  • 资助金额:
    $ 59.46万
  • 项目类别:
    Standard Grant
Structural and Functional Characterization of Cyanoglobin
蓝红蛋白的结构和功能表征
  • 批准号:
    0804005
  • 财政年份:
    2007
  • 资助金额:
    $ 59.46万
  • 项目类别:
    Continuing Grant
Structural and Functional Characterization of Cyanoglobin
蓝红蛋白的结构和功能表征
  • 批准号:
    0091182
  • 财政年份:
    2001
  • 资助金额:
    $ 59.46万
  • 项目类别:
    Continuing Grant

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