Characterization of the bacterial Arc system.

细菌 Arc 系统的表征。

• 批准号: 6548558
• 负责人: JONATHAN BECKWITH
• 金额: $ 4.03万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6548558
• 关键词: Escherichia coli; Haemophilus influenzae; Mexico; acetates; bacterial genetics; bacterial proteins; bioenergetics; biological signal transduction; cooperative study; gene expression; intermolecular interaction; lactates; membrane proteins; nucleic acid sequence; operon; oxidative stress; phosphorylation; polymerase chain reaction; protein structure function; pyruvates; quinones; site directed mutagenesis; ubiquinone; vitamin K; Escherichia coli; Haemophilus influenzae; Mexico; acetates; bacterial genetics; bacterial proteins; bioenergetics; biological signal transduction; cooperative study; gene expression; intermolecular interaction; lactates; membrane proteins; nucleic acid sequence; operon; oxidative stress; phosphorylation; polymerase chain reaction; protein structure function; pyruvates; quinones; site directed mutagenesis; ubiquinone; vitamin K

DESCRIPTION (provided by applicant) The Arc two-component signal transduction system of Escherichia coil modulates the expression of numerous operons according to the redox condition of growth. This system comprises ArcB as the sensor kinase and ArcA as the response regulator. Under reducing conditions, dimeric ArcB undergoes ATP-dependent autophosphorylation and catalyzes the phosphorylation of ArcA by a His-Asp-His-Asp phosphorelay. Phosphorylated ArcA represses transcription of numerous operons involved in aerobic respiration and activates a small number of operons involved in fermentation. D-lactate, pyruvate, and acetate stimulate ArcB autophosphorylation. Under oxidizing conditions, the accumulating ubiquinone or menaquinone inhibits ArcB autophosphorylation, thereby allowing ArcB to catalyze net dephosphorylation of ArcA-P via an Asp-His-Asp reverse relay. Characterization of the Arc system will deepen our understanding of how bacteria optimize their strategy for energy metabolism.The proposed project has three main aims. The first is to locate the quinone reception site in ArcB and define the mode of action of the signal. The second is to determine which phosphotransfer step in signal transmission and signal decay occurs intermolecularly between the two subunits of ArcB. The last objective is to explore the true role of the cytosolic PAS domain in ArcB, erroneously reported to be the receptor site for the redox signal.This research will be done primarily in Mexico as an extension of NIH grant #R01 GM40993.

描述（由申请人提供）Escherichia线圈的弧两分量信号转导系统根据生长的氧化还原条件调节了许多操纵子的表达。该系统包括ARCB作为传感器激酶，而ARCA作为响应调节剂。在还原条件下，二聚体ARCB经历了ATP依赖性自磷酸化，并通过His-Asp-His-Asp磷层催化ARCA的磷酸化。磷酸化的ARCA抑制了参与有氧呼吸的许多操纵子的转录，并激活了少数参与发酵的操纵子。 D-乳酸，丙酮酸和醋酸酯刺激ARCB自磷酸化。在氧化条件下，累积的泛酮或甲酸苯丙胺会抑制ARCB自磷酸化，从而允许ARCB通过ASP-HIS-ASP反向继电器催化ARCA-P的净脱磷酸化。 ARC系统的表征将加深我们对细菌如何优化其能源代谢策略的理解。拟议的项目具有三个主要目的。首先是在ARCB中定位喹酮接收位点并定义信号的作用方式。第二个是确定信号传递中的磷酸转移步骤和信号衰减的哪个步骤是在ARCB的两个亚基之间进行的。最后一个目标是探索胞质PAS结构域在ARCB中的真正作用，错误地据报道是氧化还原信号的受体位点。这项研究将主要在墨西哥进行，作为NIH授予＃R01 GM40993的扩展。