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艾米丽韦纳特博士、埃默里大学的克莉丝汀邓纳姆博士和马奎特大学的詹姆斯金凯德博士研究细菌氧敏感蛋白。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，并且已经进化以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却知之甚少。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，它考察了一个称为球蛋白偶联传感器的蛋白质家族的信号传导机制和途径，该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，该项目的参与者正在将他们的研究成果整合到棋盘游戏中，以创建课程计划，使小学和中学生意识到蛋白质如何帮助细菌感知和应对环境变化。 该研究项目旨在表征分子内和分子间的蛋白质相互作用，这些蛋白质相互作用通过称为球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。球蛋白偶联传感器蛋白广泛分布于细菌内，并含有与重要表型（包括生物膜形成、运动性和毒力）相关的输出结构域。包括诱变/筛选、酶动力学、共振拉曼光谱和X射线晶体学的研究方法的组合被用于询问珠蛋白偶联传感器蛋白内的氧依赖性信号传导机制以及信号传导事件向下游伙伴的传输。这项研究的结果有望提供有关细菌气敏蛋白、信号转导途径和控制生物膜形成和毒力的关键细菌酶域的调控的新信息。该奖项反映了NSF的法定使命，并被认为值得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来支持。

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 are integrating their research results into a board game to 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 are expected to 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.