Neisseria gonorrhoeae G4-binding proteins that regulate pilin antigenic variation

调节菌毛蛋白抗原变异的淋病奈瑟菌 G4 结合蛋白

• 批准号: 8230217
• 负责人: Ella Rose Rotman
• 金额: $ 5.22万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8230217
• 关键词: Affect; Affinity; Affinity Chromatography; Antigenic Variation; Binding; Binding Proteins; Cells; Chromosomes; Crude Extracts; DNA Structure; Drug Delivery Systems; Event; Fellowship; Fimbriae Proteins; Fluorescence; Fluorescence Anisotropy; Gel; Gene Conversion; Genes; Genetic Recombination; Goals; Gonorrhea; Guanine; Homologous Gene; Human; Immune system; Immunity; Mass Spectrum Analysis; Neisseria gonorrhoeae; Organism; Pathway interactions; Pilum; Play; Protein Binding; Proteins; Resolution; Role; Sexually Transmitted Diseases; Streptavidin; Structure; Surface; Virulence Factors; Work; helicase; in vivo; loss of function; mutant; novel; nuclease; pathogen; pathogenic bacteria; pilus genes; prevent; promoter; public health relevance

DESCRIPTION (provided by applicant): Antigenic variation of the N. gonorrhoeae pilus is one of the reasons why long term immunity is difficult to achieve, as hosts can get reinfected. Av is dependent on both the RecF-like recombination pathway and the formation of a G4 structure upstream of the pilE promoter, but the exact mechanism is still unknown. The role of G4 structures in the cell is still controversial and understanding how the pilE G4 affects antigenic variation would help G4 structures to be accepted as biologically relevant. The goal of this project is to identify and characterize the proteins that assist in formation, stability, and resolution of the pilE G4 DNA structure in vivo. One of these new proteins could be a potential drug target for preventing recurring gonococcal infections. PUBLIC HEALTH RELEVANCE: By changing their surface pili, the pathogenic bacterium Neisseria gonorrhoeae can infect previously cured hosts. Pilin antigenic variation is a gene conversion event that is dependent on recombination proteins as well as a 16 bp guanine quartet (G4) structure upstream of the expressed pilus gene. The work proposed in this fellowship seeks to establish whether two helicases involved in pilin antigenic variation interact specifically with the G4 structure, and to identify novel G4-binding proteins that play a role in initiating antigenic variation.

描述（由申请方提供）：N.淋病菌毛是难以实现长期免疫的原因之一，因为宿主可能会再次感染。Av依赖于RecF样重组途径和pilE启动子上游G4结构的形成，但确切的机制仍然未知。G4结构在细胞中的作用仍然是有争议的，了解pilE G4如何影响抗原变异将有助于G4结构被接受为生物学相关的。该项目的目标是鉴定和表征有助于体内pilE G4 DNA结构形成、稳定和解析的蛋白质。这些新蛋白质之一可能是预防复发性淋球菌感染的潜在药物靶点。 公共卫生相关性：通过改变其表面皮利，致病性淋病奈瑟菌可感染先前治愈的宿主。菌毛蛋白抗原变异是一种基因转换事件，它依赖于重组蛋白以及表达的菌毛基因上游的16 bp鸟嘌呤四联体（G4）结构。在这项研究中提出的工作旨在确定是否两个参与菌毛抗原变异的解旋酶与G4结构特异性相互作用，并确定新的G4结合蛋白，在启动抗原变异中发挥作用。