Core 4 Sali Echeverria

核心 4 萨利·埃切维里亚

• 批准号: 10666663
• 负责人: ANDREJ SALI
• 金额: $ 19.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666663
• 关键词: Affinity Chromatography; Algorithms; Architecture; Biochemical; Bioinformatics; Biology; CD4 Positive T Lymphocytes; CRISPR/Cas technology; Complex; Computer software; Cryoelectron Microscopy; Data; Data Analyses; Data Set; Deuterium; Development; Genetic; Genetic Transcription; Goals; HIV; HIV Infections; HIV-1; Heterogeneity; Human; Hydrogen; Individual; Integration Host Factors; Label; Lead; Maps; Mass Spectrum Analysis; Methods; Modeling; Molecular Conformation; Pathway interactions; Peptides; Post-Translational Protein Processing; Proteins; Proteomics; Resolution; Services; Statistical Data Interpretation; Structural Models; Structure; Systems Biology; Viral; Visualization; cell type; crosslink; data integration; data tools; density; flexibility; genome editing; genome-wide analysis; improved; multiple data types; mutation screening; network models; open source; particle; pathogen; protein complex; protein protein interaction; restraint; structural biology; structural determinants; success; tool

THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES COMPUTATIONAL CORE SUMMARY The overall goal of the Computational Core is to facilitate the analysis and interpretation of multiple data types across Projects and Cores to characterize the cellular networks, proteins, and protein complexes that influence HIV replication and latency. We will employ existing bioinformatics and systems biology approaches, as well as develop new methods to facilitate the unification of mechanistic and structural details with network biology, with a strong emphasis on the analysis and integration of data derived from proteomics, genetics, and structural biology approaches. Specifically, we will provide the tools to identify interactions of endogenous proviral and antiviral HIV-host protein complexes that have been structurally and functionally characterized by the Proteomics, Genetics, and Structural Biology Cores. This includes datasets from affinity purification mass spectrometry (AP-MS), native mass spectrometry (nMS), cross-linking mass spectrometry (XL-MS), hydrogen/deuterium exchange mass spectrometry (H/DX-MS), systematic genome editing by CRISPR-Cas9, deep mutational scanning (DMS), and cryo-electron microscopy (cryo-EM). These datasets will be analyzed separately as well as jointly, followed by visualization to gain a deeper understanding of the functional pathways that are modulated during HIV infection. Finally, we will determine the structures of HIV-human protein complexes by an integrative approach using various proteomics, genetics, structural, and biochemical data. Integrative structure determination will be performed using the open-source Integrative Modeling Platform (IMP) package developed in the Sali lab (Core Lead). We will initially focus on protein complexes containing human or simian A3Gs, and HIV-1 Vif, Rev, and Tat, followed by structure determination of HIV-human complexes identified from CD4+ T cells and structurally interrogated by the Proteomics Core.

HARC 中心：HIV 配件和调节复合体 计算核心 概括 计算核心的总体目标是促进多种数据类型的分析和解释 跨项目和核心来表征影响的细胞网络、蛋白质和蛋白质复合物 HIV 复制和潜伏期。我们将采用现有的生物信息学和系统生物学方法，以及 开发新方法，促进机械和结构细节与网络生物学的统一， 非常重视蛋白质组学、遗传学和结构学数据的分析和整合 生物学方法。具体来说，我们将提供工具来识别内源性原病毒和 抗病毒 HIV-宿主蛋白复合物，其结构和功能特征在于 蛋白质组学、遗传学和结构生物学核心。这包括来自亲和纯化质量的数据集 质谱 (AP-MS)、天然质谱 (nMS)、交联质谱 (XL-MS)、 氢/氘交换质谱 (H/DX-MS)、CRISPR-Cas9 系统基因组编辑、 深度突变扫描（DMS）和冷冻电子显微镜（cryo-EM）。这些数据集将被分析 单独或联合进行，然后进行可视化以更深入地了解功能途径 在 HIV 感染期间受到调节。最后，我们将确定HIV-人类蛋白质的结构 通过使用各种蛋白质组学、遗传学、结构和生化数据的综合方法来构建复合物。 将使用开源集成建模平台（IMP）进行集成结构确定 Sali 实验室（核心负责人）开发的软件包。我们首先将重点关注含有人类或 猿 A3Gs、HIV-1 Vif、Rev 和 Tat，然后确定 HIV-人类复合物的结构 从 CD4+ T 细胞中鉴定出来，并由蛋白质组学核心进行结构询问。