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
• 负责人: Juliette Lecomte
• 金额: $ 130万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1330488&HistoricalAwards=false
• 关键词: Structural; dynamic; characterization; hemoglobins

Intellectual meritThe physical properties of globular proteins are a topic of intense investigation and practical importance. Multiple approaches have been deployed to understand the determinants of stability and plasticity of these vital biomolecules. Among the methods that are most useful, but so far much underutilized, is nuclear magnetic resonance spectroscopy (NMR) at high pressure. The combination of gentle perturbation and residue-level description afforded by this technique has excellent potential for exposing novel architectural principles in proteins. The proposed research will combine molecular biology, amino acid sequence analysis, and high-pressure NMR methods to explore the native state of a set of monomeric bacterial and algal hemoglobins. The work will investigate the original notion that a common internal cavity network is a crucial entity governing conformational changes concerted with ligand binding and volume dynamics. Studies will be extended to related proteins from organisms that live in high pressure environments to enhance the description of the molecular attributes of globins functioning under extreme conditions of pressure and low temperature. Because the globins of interest are enzymatic and of ancient origin, the results will pertain to multiple fields of inquiry besides protein physical chemistry, including phylogenetics, heme chemistry, and molecular evolution. These ramifications offer an opportunity for laboratory and classroom training of students with diverse interests.Broader impactThe broader impact of the proposed research will be achieved through a combination of teaching, training, outreach, and dissemination. Research results will be incorporated in a biophysics undergraduate course in spectroscopy and in a graduate course in biophysical methods. Training will be provided to graduate and undergraduate students, including REU summer students, working directly on the project. Participation in outreach activities will include lab tours for high-school students along with research and career presentations to attract women and underrepresented groups to STEM fields. Participation in the Biophysics Research for Baltimore Teens summer program (organized by the Program in Molecular Biophysics of Johns Hopkins University) will focus on introducing selected high-school students of Baltimore City to scientific research. Dissemination will be through publications, lectures at other institutions, participation in conferences, and database depositions.

智力价值球状蛋白质的物理性质是一个具有深入研究和实际意义的话题。人们已经采用多种方法来了解这些重要生物分子的稳定性和可塑性的决定因素。在最有用的方法中，但到目前为止还没有得到充分利用的方法是高压核磁共振光谱分析(核磁共振)。这项技术提供了温和的扰动和残基水平描述的组合，在揭示蛋白质中新的结构原理方面具有很好的潜力。这项拟议的研究将结合分子生物学、氨基酸序列分析和高压核磁共振方法来探索一组单体细菌和藻类血红蛋白的天然状态。这项工作将调查最初的概念，即共同的内部空穴网络是控制与配体结合和体积动力学相协调的构象变化的关键实体。研究将扩展到生活在高压环境中的生物体的相关蛋白质，以加强对珠蛋白在极端压力和低温条件下发挥作用的分子属性的描述。由于感兴趣的球蛋白是酶的，而且起源于古代，因此除了蛋白质物理化学之外，结果还将涉及多个领域的研究，包括系统发育、血红素化学和分子进化。这些结果为具有不同兴趣的学生提供了实验室和课堂培训的机会。更广泛的影响拟议的研究将通过教学、培训、推广和传播的组合实现更广泛的影响。研究成果将被纳入光谱学的生物物理学本科课程和生物物理方法的研究生课程。将为直接参与该项目的研究生和本科生提供培训，包括REU暑期学生。参加外联活动将包括为高中生进行实验室参观，以及研究和职业介绍，以吸引妇女和代表不足的群体进入STEM领域。参加巴尔的摩青少年生物物理学研究暑期项目(由约翰·霍普金斯大学分子生物物理学项目组织)将重点介绍巴尔的摩市精选的高中生从事科学研究。将通过出版物、在其他机构的讲座、参加会议和数据库证词进行传播。

项目成果

Distal lysine (de)coordination in the algal hemoglobin THB1: A combined computer simulation and experimental study

• DOI: 10.1016/j.jinorgbio.2021.111455
• 发表时间: 2021-04-18
• 期刊: JOURNAL OF INORGANIC BIOCHEMISTRY
• 影响因子: 3.9
• 作者: Julio Plana，Laia;Martinez Grundman，Jaime E.;Capece，Luciana
• 通讯作者: Capece，Luciana

Replacement of the heme axial lysine as a test of conformational adaptability in the truncated hemoglobin THB1

替换血红素轴向赖氨酸作为截短血红蛋白 THB1 构象适应性的测试

• DOI: 10.1016/j.jinorgbio.2019.110824
• 发表时间: 2019
• 期刊: Journal of Inorganic Biochemistry
• 影响因子: 3.9
• 作者: Nye, Dillon B.;Johnson, Eric A.;Mai, Melissa H.;Lecomte, Juliette T.J.
• 通讯作者: Lecomte, Juliette T.J.

Dynamics of Lysine as a Heme Axial Ligand: NMR Analysis of the Chlamydomonas reinhardtii Hemoglobin THB1

赖氨酸作为血红素轴向配体的动力学：莱茵衣藻血红蛋白 THB1 的 NMR 分析

• DOI: 10.1021/acs.biochem.6b00926
• 发表时间: 2017
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Preimesberger, Matthew R.;Majumdar, Ananya;Lecomte, Juliette T.
• 通讯作者: Lecomte, Juliette T.

Control of distal lysine coordination in a monomeric hemoglobin: A role for heme peripheral interactions

单体血红蛋白远端赖氨酸协调的控制：血红素外周相互作用的作用

• DOI: 10.1016/j.jinorgbio.2021.111437
• 发表时间: 2021
• 期刊: Journal of Inorganic Biochemistry
• 影响因子: 3.9
• 作者: Martinez Grundman, Jaime E.;Julió Plana, Laia;Schlessman, Jamie L.;Capece, Luciana;Estrin, Darío A.;Lecomte, Juliette T.J.
• 通讯作者: Lecomte, Juliette T.J.

Hemoglobin: Some (Dis)Assembly Required

血红蛋白：需要一些（分解）组装

• DOI: 10.1016/j.bpj.2019.12.041
• 发表时间: 2020
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Lecomte, Juliette T.J.