Pittsburgh Center for HIV Protein Interactions (PCHPI)

匹兹堡 HIV 蛋白质相互作用中心 (PCHPI)

基本信息

批准号：
9270301
负责人：
ANGELA M. GRONENBORN
金额：
$ 30.4万
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 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9270301
关键词：
Acquired Immunodeficiency Syndrome Address Affect Binding Binding Proteins Biochemical Biology Capsid Cell Nucleus Cell Surface Receptors Cell physiology Cells Collaborations Communication Complex Computer Analysis Computer Simulation Cone Cryoelectron Microscopy Cyclophilin A DBL Oncoprotein Data Disease Educational workshop Event Fluorescence Fostering Funding Grant HIV HIV-1 Health Human Hybrids Image Imaging technology Immune In Vitro Individual Infection Integrase Intervention Knowledge Label Life Life Cycle Stages Mediating Membrane Fusion Methodology Methods Modeling Molecular NMR Spectroscopy National Institute of General Medical Sciences Nuclear Nuclear Import Nuclear Pore Complex Predisposition Principal Investigator Process Production Protein Dynamics Protein Family Proteins Proteomics Protocols documentation RNA interference screen RNA-Directed DNA Polymerase Recombinants Recruitment Activity Relaxation Research Resolution Reverse Transcription Roentgen Rays Role Sequence Analysis Staging Structural Biologist Structural Genes Structure TRIM Gene Techniques Technology Time Viral Viral Genome Viral Proteins Virion Virus Virus Diseases base biochemical tools biophysical techniques complex biological systems electron tomography fight against inhibitor/antagonist member new therapeutic target novel novel strategies novel therapeutic intervention nucleocytoplasmic transport physical process programs protein complex protein function research study simulation solid state nuclear magnetic resonance success technology development tool trafficking virology web site

项目摘要

DESCRIPTION (provided by applicant): Essentially every step in the HIV life cycle interfaces intimately with the host cell machinery. The Pittsburgh Center of HIV Protein Interactions will focus on the steps and interactions that occur with the host after engagement of cell surface receptors and membrane fusion and before integration of the viral genome into that of the host, the so called "early events". Several essential molecular interactions and enzymatic activities occur within this time window, necessary for productive progression of the viral life cycle. Thus, it represents a pivotal period in the infection process, during which the susceptibility of the virs to disruptive interventions is likely to be high and little explored. Broadly speaking, the processes that we will focus on include capsid disassembly (uncoating), reverse transcription, evasion of innate immune factors, and nuclear entry. Given the importance of the capsid structure and its interactions for many of these processes, we have expanded capsid studies to include an analysis of CA protein maturation and capsid formation. We plan to build on our successes and apply the extensive and complementary experimental expertise of our team to carry out 1) biochemical and high-resolution structure studies of individual proteins and complexes, 2) proteomics analyses to identify novel interactions and complexes, 3) virology and imaging studies to understand protein function in the context of the cell and virus infection, 4) sequence analyses of evolutionary correlations in protein interactions and dynamics, and 5) computational analyses to generate an all-atom model of the HIV-1 capsid and to elucidate the physical basis of uncoating (the process by which the capsid disassembles). Further, we plan to extend our Correlative Imaging Technology Development Program to develop specific probes and tools for exploring the dynamics of HIV-1 and associated proteins during cellular infection

描述（由申请人提供）：基本上，HIV 生命周期中的每一步都与宿主细胞机制密切相关。匹兹堡艾滋病毒蛋白质相互作用中心将重点研究细胞表面受体接合和膜融合之后以及病毒基因组整合到宿主基因组之前与宿主发生的步骤和相互作用，即所谓的“早期事件”。在此时间窗口内发生一些重要的分子相互作用和酶活性，这对于病毒生命周期的有效进展是必需的。因此，它代表了感染过程的关键时期，在此期间，病毒对破坏性干预措施的敏感性可能很高，但很少被研究。从广义上讲，我们将重点关注的过程包括衣壳分解（脱壳）、逆转录、先天免疫因子的逃避和核进入。鉴于衣壳结构及其相互作用对于许多这些过程的重要性，我们扩大了衣壳研究范围，包括对 CA 蛋白成熟和衣壳形成的分析。我们计划在我们的成功基础上，应用我们团队广泛且互补的实验专业知识来开展 1) 单个蛋白质和复合物的生化和高分辨率结构研究，2) 蛋白质组学分析，以确定新的相互作用和复合物，3) 病毒学和成像研究，以了解细胞和病毒感染情况下的蛋白质功能，4) 蛋白质相互作用和动力学中进化相关性的序列分析，以及 5) 计算分析，以生成 HIV-1 衣壳的全原子模型并阐明脱衣的物理基础（衣壳分解的过程）。此外，我们计划扩展我们的相关成像技术开发计划，以开发特定的探针和工具，用于探索细胞感染期间 HIV-1 和相关蛋白的动态