Cryogenic Electron Microscopy Core

摘要 单粒子低温电子显微镜（cryo-EM）通过其能力彻底改变了结构生物学 解决和阐明许多大分子复合物的结构， 不受结构研究的影响在过去的几年里，越来越明显的是， 低温-EM的固有优点使其更适合于某些大分子的结构研究， 特别是那些大的、动态的、难以纯化的和/或生物化学性能差的。Cryo-EM具有 因此迅速成为结构生物学的中流砥柱。Core 1将采用最新一代工具， 单粒子冷冻EM，用于专门解决与HIVE P50相关的结构问题 中心这些工具将用于解决与艾滋病毒有关的大分子复合物的结构 生命周期，包括病毒复制，整合，组装和成熟，并将因此扩大不断演变的 与HIV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 促进抗逆转录病毒疗法的改进，并导致更好地了解病毒耐药性。的 Cryo-EM核心将：提供基本服务，将评估样品质量和高分辨率的可行性 研究，将提供给所有HIVE成员的服务;提供结构生物学方面的先进专业知识 与几位主要研究人员合作，共同推动高分辨率结构测定;应用 根据需要，将正在进行的或新的技术开发用于特定项目。核心1将因此高度 互动内，和一个组成部分，蜂巢中心，并将协调与所有调查人员， 不同程度。

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.