Building quaternary structure in heme proteins

蛋白质是基本的生物分子，作为个体实体（蛋白质单体）或组合（二聚体、三聚体、四聚体等）发挥作用。蛋白质单体成为高阶组装的一部分的能力对生物学至关重要，但到目前为止，我们对复杂蛋白质组装如何从简单单体进化而来的理解仍然有限。一种众所周知的蛋白质是人类血红蛋白，它是一种精确调节氧气运输的四聚体。凭借这一奖项，生命过程化学项目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的必要修饰。研究的重点是来自单细胞生物和耐热性增强的人工蛋白质的血红蛋白。该研究采用计算和实验相结合的方法来研究血红蛋白。进行研究的大学水平的学生精通生物物理方法的使用。另一项工作是将研究结果整合到生物化学和生物物理化学的本科课程中。来自巴尔的摩市和周边地区的高中学生被勒孔特博士和她的学生在推广活动中参与科学调查。截断血红蛋白（TrHbs）是一种具有酶活性的小蛋白质，与活性氧和活性氮的加工有关。一些TrHbs在水溶液中呈多聚体状态，表明其过渡到具有配合配体结合特性的组装体。研究的重点是这种多聚态的分析和设计。起点是来自嗜压菌希瓦氏菌和绿藻莱茵衣藻的自然序列，以及来自多个序列比对的人工超稳定序列。电子吸收和核磁共振光谱用于检查新生二聚体的性质和亚基结合配体结合的后果。该研究为多聚体蛋白的进化及其热力学性质的控制提供了基础信息。该奖项反映了美国国家科学基金会的法定使命，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。

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.