Cryogenic Electron Microscopy Core

低温电子显微镜核心

• 批准号: 10242902
• 负责人: Dmitry Lyumkis
• 金额: $ 50.9万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242902
• 关键词: Address; Anisotropy; Automobile Driving; Biochemical; Biological; Biology; Classification; Collaborations; Complex; Core Facility; Coupled; Cryoelectron Microscopy; Crystallization; Data; Data Collection; Development; Docking; Electron Microscopy; Evolution; Future; Generations; Goals; HIV; HIV Infections; Heterogeneity; Image Analysis; Knowledge; Label; Lead; Macromolecular Complexes; Maps; Methods; Mind; Modeling; Molecular; Molecular Structure; Paper; Phase; Process; Proteins; Protocols documentation; RNA; Research Personnel; Resolution; Resource Sharing; Ribosomes; Sampling; Services; Specimen; Standardization; Structure; Techniques; Technology; Time; Viral; Virus Replication; Vision; X-Ray Crystallography; antiretroviral therapy; base; computerized data processing; cryogenics; data acquisition; density; experience; image processing; insight; instrument; laboratory experience; macromolecule; member; molecular modeling; new technology; novel; novel strategies; operation; particle; screening; structural biology; tool; viral resistance

ABSTRACT Single-particle cryogenic-electron microscopy (cryo-EM) has revolutionized structural biology through its ability to tackle and elucidate structures of numerous macromolecular complexes that have previously been impervious to structural studies. Over the last several years, it has become increasingly clear that some inherent advantages in cryo-EM make it more suitable to structural studies of certain macromolecules, especially those that are large, dynamic, difficult to purify, and/or poorly biochemically behaved. Cryo-EM has therefore quickly become a mainstay in structural biology. Core 1 will employ the latest generation tools in single-particle cryo-EM for the purpose of specifically addressing structural questions relevant to the HIVE P50 center. The tools will be used to solve structures of macromolecular complexes that are involved in the HIV lifecycle, including viral replication, integration, assembly, and maturation, and will thus expand the evolving structural knowledge underlying the molecular processes associated with HIV infection. This in turn will broadly facilitate the improvement of antiretroviral therapies and lead to a better understanding of viral resistance. The Cryo-EM core will: provide basic services that will evaluate sample quality and feasibility of high-resolution studies, a service that will be available to all HIVE members; provide advanced expertise in structural biology to jointly drive high-resolution structure determination in collaboration with several key investigators; apply ongoing or novel technical developments to specific projects on a per-need basis. Core 1 will thus be highly interactive within, and an integral part of, the HIVE center and will coordinate with all its investigators to different extents.

摘要 单粒子低温电子显微镜(Cryo-EM)通过其能力使结构生物学发生了革命性的变化 来解决和阐明许多以前被 不受结构研究的影响。在过去的几年里，越来越明显的是，一些人 低温EM的固有优势使其更适合于某些大分子的结构研究， 尤其是那些大的、动态的、难以提纯的和/或生化行为不佳的。Cryo-EM有 因此迅速成为结构生物学的中流砥柱。Core 1将采用最新一代的 用于专门解决与HIVE P50相关的结构问题的单粒子低温EM 中间。这些工具将被用来解决与艾滋病毒有关的大分子复合体的结构 生命周期，包括病毒复制、整合、组装和成熟，从而将扩大进化中的 与艾滋病毒感染相关的分子过程的基础结构知识。这反过来又将广泛地 促进改进抗逆转录病毒治疗，并导致更好地了解病毒耐药性。这个 CRYO-EM核心：提供评估样品质量和高分辨率可行性的基本服务 研究，这项服务将为所有蜂群成员提供；提供结构生物学方面的高级专业知识 与几个关键研究人员合作，共同推动高分辨率结构确定；应用 根据需要对特定项目进行持续的或新颖的技术开发。因此，核心1将高度 在蜂巢中心内进行互动，并将与其所有调查人员协调 程度不同。