Collaborative Research: Heme Distortion and Protein-Protein Contacts in Oxygen-Dependent Globin Coupled Sensor Signaling

有了这个奖项，化学部的生命过程化学项目资助了宾夕法尼亚州立大学的Emily Weinert博士、埃默里大学的Christine Dunham博士和马奎特大学的James Kincaid博士来研究细菌氧感应蛋白。细菌是生态系统、植物、动物和人类健康不可或缺的组成部分，并且已经进化到适应其环境中不断变化的条件。然而，细菌感知和响应环境气体水平变化的机制尚不清楚。该奖项支持的研究考察了环境信号在控制细菌表型中的作用；更具体地说，它研究了一组蛋白质的信号机制和途径，这些蛋白质被称为球蛋白偶联传感器，负责感知氧气。该项目为学生提供蛋白质化学、光谱学和x射线晶体学方面的专业培训。此外，该项目的参与者将研究结果整合到棋盘游戏中，并制定课程计划，使中小学生了解蛋白质如何帮助细菌感知和应对环境变化。本研究项目旨在描述通过称为珠蛋白偶联传感器的细菌血红素蛋白家族控制氧依赖性信号的分子内和分子间蛋白质相互作用。珠蛋白偶联传感器蛋白广泛分布于细菌中，并包含与重要表型相关的输出结构域，包括生物膜形成、运动性和毒力。包括诱变/筛选、酶动力学、共振拉曼光谱和x射线晶体学在内的研究方法组合被用于询问珠蛋白偶联传感器蛋白中的氧依赖信号机制以及信号事件向下游伙伴的传递。本研究的结果为细菌气敏蛋白、信号转导途径以及参与控制生物膜形成和毒力的关键细菌酶结构域的调控提供了新的信息。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。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Emily Weinert from Pennsylvania State University, Dr. Christine Dunham from Emory University, and Dr. James Kincaid from Marquette University to investigate bacterial oxygen sensing proteins. Bacteria are integral to the health of ecosystems, plants, animals, and humans, and have evolved to adapt to constantly changing conditions within their environment. However, the mechanisms by which bacteria sense and respond to changes in the levels of environmental gases are poorly understood. The research supported by this award examines the roles of environmental signals in controlling bacterial phenotypes; more specifically it examines the signaling mechanism and pathway of a family of proteins termed globin coupled sensors that are responsible for sensing oxygen. This project provides specialized training for students in protein chemistry, spectroscopy, and X-ray crystallography. Additionally, the participants in this project integrate research results into a board game and create lesson plans that make elementary and middle school students aware of how proteins help bacteria sense and react to changes in their environment. This research project seeks to characterize the intra- and inter-molecular protein interactions that control oxygen-dependent signaling by a family of bacterial heme proteins termed globin coupled sensors. Globin-coupled sensor proteins are widely distributed within bacteria and contain output domains that are linked to important phenotypes, including biofilm formation, motility, and virulence. A combination of research methods that includes mutagenesis/screening, enzyme kinetics, resonance Raman spectroscopy, and X-ray crystallography is being used to interrogate the oxygen-dependent signaling mechanism within globin coupled sensor proteins and the transmission of the signaling events to downstream partners. Results from this study provide new information about bacterial gas-sensing proteins, signal transduction pathways, and regulation of key bacterial enzymatic domains involved in controlling biofilm formation and virulence.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.