Structural Analysis of a Conserved Alphaproteobacterial Stress Response Pathway

保守的α变形菌应激反应途径的结构分析

• 批准号: 8997110
• 负责人: Jonathan W Willett
• 金额: $ 5.46万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2017-01-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8997110
• 关键词: Affect; Affinity; Alphaproteobacteria; Bacteria; Binding; Binding Sites; Biochemical; Biological Assay; Biological Models; Biophysics; C-terminal; Caulobacter; Caulobacter crescentus; Cells; Chemicals; Crystallization; Data; Discipline; Environment; Faculty; Family; Fluorescence Resonance Energy Transfer; Fluorides; Foundations; Gene Expression; Genetic; Genetic Transcription; Goals; Growth; Health; Hybrids; In Vitro; Infection; Measures; Methods; Microbial Biofilms; Microbial Physiology; Modeling; Molecular; Molecular Conformation; Mutagenesis; N-terminal; NMR Spectroscopy; Oxidative Stress; Pathogenesis; Pathway interactions; Phenotype; Phosphorylation; Phosphotransferases; Play; Positioning Attribute; Property; Protein Region; Proteins; Proteobacteria; Regulation; Reporter; Research; Roentgen Rays; Role; Sigma Factor; Signal Pathway; Signal Transduction; Signaling Protein; Stress; Structure; Surface Plasmon Resonance; Symbiosis; System; Techniques; Testing; Transcriptional Regulation; Virulence Factors; X-Ray Crystallography; base; biological adaptation to stress; biophysical analysis; biophysical techniques; genetic regulatory protein; high risk; in vivo; inorganic phosphate; interdisciplinary approach; microbial; mutant; novel; pathogen; polypeptide; post-doctoral training; protein structure; research study; response; stability testing; stressor; structural biology; yeast two hybrid system

DESCRIPTION (provided by applicant): Bacterial cells utilize both two-component signaling proteins and alternative sigma (σ) factors to modulate transcription in response to environmental stress. These environmental stress regulatory proteins are known to function as essential virulence factors in numerous bacterial pathogens. Bacterial stress responses play a fundamental role in bacterial growth, biofilm formation, pathogenesis and symbiosis. My proposed structural studies on the Caulobacter crescentus general stress signaling pathway, which integrates feature of two-component signaling and alternative s regulation, will significantly enhance our understanding of the molecular and structural basis of stress adaptation in the alphaproteobacteria. The Crosson lab has a successful track record utilizing techniques from a wide range of disciplines to pursue questions focused on molecular microbial physiology. Their broad interdisciplinary approaches promise to provide a more complete understanding of how bacterial cells can perceive and adapt to changes within their environment. My postdoctoral training in the Crosson Lab, focused on molecular biophysics and structural biology of the PhyR, σT and NepR proteins, will facilitate my successful transition into an independent faculty position, where my research will center on molecular aspects of microbial signaling.

描述（由申请人提供）：细菌细胞利用双组分信号蛋白和替代σ（σ）因子来调节转录以响应环境应激。已知这些环境应激调节蛋白在许多细菌病原体中作为必需的毒力因子起作用。细菌应激反应在细菌生长、生物膜形成、致病和共生中起着重要作用。新月柄杆菌（Caulobacter crescentus）的一般应激信号通路具有双组分信号和交替调节的特征，对这一信号通路的结构研究将极大地加深我们对α-变形菌应激适应的分子和结构基础的理解。克罗森实验室有一个成功的跟踪记录，利用来自广泛学科的技术来追求专注于分子微生物生理学的问题。他们广泛的跨学科方法有望更全面地了解细菌细胞如何感知和适应环境中的变化。我在克罗森实验室的博士后培训，专注于PhyR，σT和NepR蛋白的分子生物物理学和结构生物学，将促进我成功过渡到一个独立的教师职位，在那里我的研究将集中在微生物信号的分子方面。