Project 4: Capsid and nuclear import/integration co-factors

项目 4：衣壳和核输入/整合辅助因子

• 批准号: 10219102
• 负责人: Zandrea Ambrose
• 金额: $ 30.2万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-27 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219102
• 关键词: Amino Acids; Area; Binding; Biochemical; Biology; C-terminal; Capsid; Capsid Proteins; Cell Nucleus; Cells; Cellular biology; Collaborations; Complex; Cryoelectron Microscopy; Crystallization; Cytoplasm; Dependence; Event; HIV; HIV-1; Human; Image; Imaging technology; Infection; Integration Host Factors; Karyopherins; Label; Length; Life Cycle Stages; Link; Mediating; Mediator of activation protein; Microtubule-Organizing Center; Movement; N-terminal; Nuclear Import; Nuclear Pore Complex Proteins; Peptides; Play; Polyadenylation; Primate Lentiviruses; Primates; Production; Proteins; Recombinants; Resolution; Roentgen Rays; Role; Site; Structure; TRIM Gene; Time; Transport Process; Viral; Virus Replication; X-Ray Crystallography; Zoonoses; cold temperature; novel; nucleocytoplasmic transport; particle; protein complex; structural biology; trafficking; virus host interaction

P4. Abstract HIV-1 nuclear import is facilitated by the viral capsid protein (CA), interacting with several key cellular factors. However, the precise roles of each of these interactions in the trafficking of the viral RTC/PIC toward the nucleus and from the microtubule organizing center into the nucleus are poorly understood. We will utilize advanced imaging technology and specifically labeled viral and cellular proteins to track CA and RTC/PIC movements and interactions in real time, which will reveal hitherto unknown details of the early events of HIV- 1 biology that underlie viral trafficking, uncoating, nuclear import, and integration. We also will solve novel structures of viral-host protein complexes that are involved in the nuclear transport process, including CA in complex with NUP358, NUP153, and CPSF6 proteins, the latter also in complex with its β-karyopherin binding partner TNPO3. The completion of Project 4 will yield novel information on the virus-host interactions that underlie the key early events of the HIV-1 lifecycle at both the cell- and atomic levels.

P4.摘要 HIV-1核输入由病毒衣壳蛋白（CA）促进，与几个关键的细胞因子相互作用。 然而，这些相互作用中的每一种在病毒RTC/PIC向靶细胞运输中的确切作用是不确定的。 细胞核和从微管组织中心进入细胞核的过程知之甚少。我们将利用 先进的成像技术和特异性标记的病毒和细胞蛋白，以跟踪CA和RTC/PIC 运动和相互作用在真实的时间，这将揭示迄今未知的细节，早期事件的艾滋病毒- 1生物学的基础病毒贩运，脱壳，核进口，和整合。我们也将解决小说 参与核转运过程的病毒-宿主蛋白质复合物的结构，包括 与NUP 358、NUP 153和CPSF 6蛋白复合，后者也与其β-核转运蛋白结合复合 合作伙伴TNPO 3.项目4的完成将产生关于病毒-宿主相互作用的新信息， 在细胞和原子水平上构成了HIV-1生命周期的关键早期事件。