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Building quaternary structure in heme proteins

构建血红素蛋白的四级结构

基本信息

批准号：
2003950
负责人：
Juliette Lecomte
金额：
$ 53.6万
依托单位：
Johns Hopkins University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003950&HistoricalAwards=false
关键词：
Building quaternary structure heme proteins

项目摘要

Proteins are essential biological molecules that function as individual entities (protein monomers) or assemblies (dimers, trimers, tetramers, etc.). The ability of a protein monomer to become a part of a higher-order assembly is essential to biology, but to date, we still have only a limited understanding of how complex protein assemblies have evolved from simple monomers. A well-known protein is human hemoglobin, a tetramer which is precisely tuned for oxygen transport. With this award, the Chemistry of Life Processes Program in Chemistry is funding Dr. Juliette Lecomte of Johns Hopkins University to explore the modifications necessary to transform monomeric hemoglobins into dimeric assemblies endowed with new chemical properties. The hemoglobins that will be at the focus of the study are from unicellular organisms and artificial proteins with enhanced thermal resistance. The research applies a combined computational and experimental approach to the study of the hemoglobins. The university-level students who conduct the research become versed in the use of biophysical methods. An additional effort is directed to the integration of the results of the research into undergraduate courses in biochemistry and biophysical chemistry. High-school students from Baltimore City and surrounding areas are engaged by Dr. Lecomte and her students in scientific investigation during outreach activities.Truncated hemoglobins (TrHbs) are small proteins endowed with enzymatic activity related to the processing of reactive oxygen and nitrogen species. Some TrHbs adopt or sample a multimeric state in aqueous solution, suggesting a transition to an assembly with cooperative ligand binding properties. The focus of the research is the analysis and design of such multimeric states. Starting points are natural sequences from the piezophile Shewanella benthica and the green alga Chlamydomonas reinhardtii, and artificial hyperstable sequences derived from multiple sequence alignments. Electronic absorption and nuclear magnetic resonance spectroscopies are used to inspect nascent dimeric properties and the consequences of subunit association for ligand binding. The study provides fundamental information on the evolution of multimeric proteins and the control of their thermodynamic properties.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

蛋白质是作为个体实体（蛋白质单体）或组装体（二聚体、三聚体、四聚体等）发挥功能的基本生物分子。蛋白质单体成为高阶组装体一部分的能力对生物学至关重要，但迄今为止，我们对复杂蛋白质组装体如何从简单单体进化而来的了解仍然有限。一种众所周知的蛋白质是人类血红蛋白，它是一种四聚体，可以精确地调节氧气的运输。有了这个奖项，化学生命过程计划的化学正在资助约翰霍普金斯大学的Juliette Lecomte博士探索将单体血红蛋白转化为具有新化学性质的二聚体组装所需的修饰。将成为研究重点的血红蛋白来自单细胞生物和具有增强耐热性的人工蛋白质。本研究采用计算和实验相结合的方法来研究血红蛋白。进行研究的大学生精通生物物理方法的使用。一个额外的努力是针对整合的研究结果到本科生课程的生物化学和生物物理化学。来自巴尔的摩市及周边地区的高中生在Lecomte博士和她的学生的外展活动中参与科学调查。截短血红蛋白（TrHbs）是一种小蛋白，具有与活性氧和氮的加工相关的酶活性。一些TrHb在水溶液中采用或采样多聚体状态，表明过渡到具有合作配体结合特性的组装体。研究的重点是这种多聚体状态的分析和设计。起始点是来自嗜压菌Shewanella benthica和绿色嗜压菌Chlamydiumreinhardtii的天然序列，以及来自多序列比对的人工超稳定序列。电子吸收和核磁共振光谱被用来检查新生的二聚体的性质和亚基协会的配体结合的后果。该研究提供了关于多聚体蛋白质进化及其热力学性质控制的基本信息。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.

Architectural digest: Thermodynamic stability and domain structure of a consensus monomeric globin