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Project 1: Structure and dynamics of Gag maturation intermediates and mechanisms of viral genome enclosure

项目1：Gag成熟中间体的结构和动力学以及病毒基因组封装机制

基本信息

批准号：
9977949
负责人：
Tatyana Polenova
金额：
$ 24.21万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-27 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9977949
关键词：
Antiviral Agents Binding Biochemical Bioinformatics Capsid Capsid Proteins Complex Cryo-electron tomography Cryoelectron Microscopy Cyclophilin A Data Data Set Defect Ensure Genomics HIV HIV-1 Illinois Impairment Integrase Integrase Inhibitors Laboratories Lead Length Letters Magic Maps Membrane Mesylates Methodology Methods Modeling Molecular Conformation Morphogenesis Morphology Mutation NMR Spectroscopy Peptides Phenotype Play Positioning Attribute Preparation Process Production Proteins RNA Reporting Resolution Ribonucleoproteins Role Series Structure Testing Tomogram United States National Institutes of Health Universities Viral Viral Genome Virus Work analog density drug development experimental study gag Gene Products inhibitor/antagonist insight milligram molecular dynamics mutant particle simulation small molecule small molecule inhibitor solid state viral RNA viral genomics virology

项目摘要

P1. Abstract Virus maturation is critical for HIV-1 replication and occurs through an orchestrated series of Gag and Gag-Pol cleavages that result in formation of the conical viral capsid enclosing the viral genomic ribonucleoprotein complex. HIV-1 maturation represents an attractive target for antiviral drug development as evidenced by studies of the small molecule inhibitor bevirimat. In this project, we will employ structural, biochemical, and virological methods to generate new insights into the structure and dynamics of the immature Gag lattice and the effects of maturation inhibitors. We will also define the mechanism by which Integrase-RNA interactions localize the RNP within the viral capsid. Finally, we will dissect the mechanism by which uncleaved matrix-capsid interferes with HIV-1 maturation. These studies will reveal new fundamental aspects of HIV-1 maturation and its inhibition.

P1。摘要病毒成熟是HIV-1复制的关键，通过一系列精心安排的Gag和Gag-Pol裂解发生这导致形成包裹病毒基因组核糖核蛋白复合体的锥形病毒衣壳。HIV-1 成熟是抗病毒药物开发的一个有吸引力的目标，小分子的研究证明了这一点。抑制剂倍维力马特。在这个项目中，我们将使用结构、生化和病毒学方法来产生新的对未成熟的Gag晶格的结构和动力学以及成熟抑制剂的影响的见解。我们还将确定整合酶-RNA相互作用在病毒衣壳内定位RNP的机制。最后，我们会剖析未裂解的基质衣壳干扰HIV-1成熟的机制。这些研究将揭示新的 HIV-1成熟及其抑制的基本方面。