Molecular Mechanism of Pathogenesis

发病机制的分子机制

基本信息

批准号：
7058321
负责人：
JACK E DIXON
金额：
$ 36.55万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-15 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7058321
关键词：
Agrobacterium Pseudomonas Yersinia pestis bacterial cytopathogenic effect bacterial proteins biological signal transduction cysteine endopeptidases enzyme substrate fatty acylation green fluorescent proteins hypersensitivity immunoprecipitation mass spectrometry myristates phosphorylation posttranslational modifications protein localization protein structure function proteolysis virulence yeast two hybrid system

Agrobacterium Pseudomonas Yersinia pestis bacterial cytopathogenic effect bacterial proteins biological signal transduction cysteine endopeptidases enzyme substrate fatty acylation green fluorescent proteins hypersensitivity immunoprecipitation mass spectrometry myristates phosphorylation posttranslational modifications protein localization protein structure function proteolysis virulence yeast two hybrid system

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项目摘要

DESCRIPTION (provided by applicant): A Yersinia effector known as YopT and a Pseudomonas avirulence protein known as AvrPphB define a family of 19 proteins involved in bacterial pathogenesis. We show that both YopT and AvrPphB are cysteine proteases, and their proteolytic activities are dependent upon the invariant C/HID residues conserved in the entire YopT family. YopT cleaves the post-translationally modified Rho GTPases near their carboxyl termini, releasing them from the membrane. This leads to the disruption of actin cytoskeleton in host cells. The proteolytic activity of AvrPphB is essential for autoproteolytic cleavage of an AvrPphB precursor as well as for eliciting the hypersensitive response in plants. The biochemical functions of most avirulence (Avr) proteins are unknown. This proposal focuses on developing a molecular understanding of how the AvrPphB family of proteins is activated and post-translationally modified. In addition, efforts to identify the substrate(s) for AvrPphB are described. Finally, we propose to obtain the x-ray structure of AvrPphB complexed with a peptide substrate. These experiments will provide us with new insights into the molecular mechanism of pathogenesis.

描述（由申请人提供）：一种称为YOPT的Yersinia效应子和称为Avrpphb的假单胞菌促进蛋白，定义了与细菌发病机理有关的19个蛋白质家族。我们表明，Yopt和Avrpphb都是半胱氨酸蛋白酶，它们的蛋白水解活性取决于整个Yopt家族中保守的不变C/HID残基。 Yopt在其羧基末端附近裂解了翻译后修饰的Rho GTPase，从膜上释放出来。这导致宿主细胞中肌动蛋白细胞骨架的破坏。 AVRPPHB的蛋白水解活性对于AVRPPHB前体的自负解释以及引起植物中的超敏反应至关重要。大多数活力（AVR）蛋白的生化功能尚不清楚。该提案着重于对蛋白质蛋白的AVRPPHB家族如何被激活和翻译后修饰的分子理解。此外，描述了确定AVRPPHB底物的努力。最后，我们建议获得与肽底物复合的AVRPPHB的X射线结构。这些实验将为我们提供有关发病机理分子机制的新见解。