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首页> 外文学位 >Design and signaling mechanisms of PAS sensor proteins: How cells sense and respond to their environment.
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Design and signaling mechanisms of PAS sensor proteins: How cells sense and respond to their environment.

机译：PAS传感器蛋白的设计和信号传导机制：细胞如何感知和响应其环境。

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摘要

Signal transduction networks mediate cellular responses to environmental stimuli. These signals may be chemical or physical in nature and include light, chemical ligands and electric field. My thesis addresses how signals are transmitted at the molecular level by a family of sensor proteins containing Per-ARNT-Sim (PAS) sensor domains. PAS sensor domains comprise a superfamily of more than 20,000 members found in all kingdoms of life. Interestingly, despite having a conserved fold, PAS domains recognize and respond to a range of signals including light, oxygen and redox potential and couple these signal inputs to output behaviors either directly or indirectly, through an associated effector domain. The widespread and modular nature of PAS sensor proteins, and their ability to sense many different types of environmental stimuli and linkage to a wide range of effector (output) domains, make them an ideal system for studying the rules governing signal transduction in cells and remodeling input/output (I/O) signaling processes of cells.;PAS sensor proteins represent a toolkit of "plug-and-play" parts (i.e., modules or domains) that can be used to remodel cellular behavior. For example, the PAS sensor protein FixL from Bradyrhizobium japonicum (BjFixL), which mediates nitrogen fixation in root nodules of plants, is comprised of an oxygen-sensitive heme PAS domain covalently linked to a second N-terminal PAS domain and a C-terminal histidine kinase effector domain. On the other hand, a photosensory PAS domain from Bacillus subtilis YtvA (BsYtvA-LOV), linked N-terminally to a STAS domain, binds FMN and senses light. By replacing the heme PAS sensor domain of BjFixL with BsYtvA-LOV, the signaling specificity of BjFixL can be switched from oxygen to light (Moglich et al., 2009a).;In this thesis, I address multiple aspects of PAS sensor protein signaling including: (i) the role of quaternary structure in the signaling mechanisms of PAS sensor proteins, (ii) engineering novel two-input PAS sensor proteins, (iii) the development of a light-regulated transcription system in Escherichia coli on the basis of an engineered, light-sensitive, PAS sensor kinase, and (iv) the identification of an evolutionarily-conserved network of residues in PAS domains that may form the basis of structural and functional similarities among members of the PAS domain superfamily.;Understanding how PAS sensor proteins signal will inform the underlying signaling networks that govern cell morphology, seed germination, phototaxis, and many other physiological behaviors. Moreover, these rules may be used to engineer novel protein sensors that, when integrated into a cellular system, re-wire the response of a cell to an environmental signal.
机译：信号转导网络介导细胞对环境刺激的反应。这些信号本质上可以是化学或物理信号，包括光，化学配体和电场。我的论文探讨了信号如何通过含有Per-ARNT-Sim（PAS）传感器域的传感器蛋白家族在分子水平上传递。 PAS传感器域包括在所有生命王国中发现的20,000多个成员的超家族。有趣的是，尽管具有保守的折叠，PAS域仍能识别并响应一系列信号，包括光，氧和氧化还原电势，并将这些信号输入通过关联的效应子域直接或间接耦合至输出行为。 PAS传感器蛋白的广泛和模块化性质，以及它们感测许多不同类型的环境刺激以及与多种效应子（输出）域链接的能力，使其成为研究控制细胞信号转导和重构规则的理想系统PAS传感器蛋白代表“即插即用”部分（即模块或域）的工具包，可用于重塑细胞行为。例如，来自日本根瘤菌的PAS传感器蛋白FixL（BjFixL）介导植物根瘤中的氮固定，由对氧敏感的血红素PAS域共价连接到第二个N端PAS域和一个C端组成组氨酸激酶效应域。另一方面，来自枯草芽孢杆菌YtvA的光敏PAS域（BsYtvA-LOV）在N端连接到STAS域，与FMN结合并感应光。通过用BsYtvA-LOV取代BjFixL的血红素PAS传感器结构域，可以将BjFixL的信号特异性从氧气转换为光（Moglich et al。，2009a）。 ：（i）四级结构在PAS传感器蛋白信号传导机制中的作用，（ii）工程化新型的双输入PAS传感器蛋白，（iii）在大肠杆菌的基础上开发光调节转录系统工程化的，光敏感的PAS传感器激酶，以及（iv）鉴定PAS域中残基的进化保守网络，这些网络可能构成PAS域超家族成员之间结构和功能相似性的基础。蛋白质信号将通知控制细胞形态，种子萌发，趋光性和许多其他生理行为的潜在信号网络。此外，这些规则可用于设计新型蛋白质传感器，将其整合到细胞系统中后，可将细胞对环境信号的响应重新关联。

著录项

  • 作者

    Ayers, Rebecca A.;

  • 作者单位

    The University of Chicago.;

  • 授予单位 The University of Chicago.;
  • 学科 Chemistry Biochemistry.;Engineering Biomedical.;Biology Bioinformatics.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 263 p.
  • 总页数 263
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 宗教;
  • 关键词

  • 入库时间 2022-08-17 11:38:24

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