Driving Biomedical Projects Portfolio of the Resource for Native MS Guided Structural Biology

蛋白质通常通过作为多个蛋白质的集合工作来执行其功能，无论是否有其他 结合的生物分子或配体。蛋白质复合体/组装体的特征，包括鉴定所有 结合伙伴，它们在复杂的体系结构/拓扑中的结合和构象变化 合作伙伴之间的相对结合亲和力是更好地理解这些复杂性的关键 系统执行其正常的生物功能，以及架构的改变如何导致故障。 MS正在成为结构生物学的强大工具，多种MS方法的组合使 生物大分子的结构表征。然而，MS仪器和MS仪器的发展 方法是充分实现利用MS进行常规、可靠、快速的结构表征 学习。推动天然MS用于结构生物学应用的技术开发，并 说明天然多发性硬化症如何指导和整合其他结构生物学方法，我们已经确定 存在重大技术挑战的三种主要蛋白质复合体，迫使PI 使用多种结构生物学方法。它们是：1)蛋白质，2)膜蛋白和膜 蛋白质：脂类复合体，以及3)RNA：蛋白质，复合体。DBP被选为包含以下项目的对象 高度的生物医学意义，其中进步取决于解决重大的技术挑战。这些 项目将从改进的本地微软工作流程中受益匪浅。解决其结构性挑战，在 他们使用的其他结构工具的上下文，也将提供适用于 研究人员的范围要广得多。有效的沟通是脱贫攻坚战取得进展的关键，以便 资源充分了解正在解决的生物问题的性质，因此合作 调查人员充分了解每种技术的当前能力。最初的项目会议有 为每一个DBP举行了一次会议，并获得了初步数据。将定期举行会议，以 评估进展并计划未来的实验。将鼓励DBP调查人员及其小组 在他们参加的会议上介绍工作，并适当地确认 网管SB资源。 当DBP达到多个高质量的 手稿准备和出版，DBP的问题可以用那里现有的技术来回答 阶段，DBP不再推动资源改进本地MS技术。资源将 参与编写和准备每一份相关的联合手稿。用于出版、期刊 将是具有高影响力并被广大社区阅读的目标，这有助于我们的传播 将这项技术推广到包括结构生物学家和生物医学研究人员在内的广泛受众的计划。

Proteins often carry out their functions by working as assemblies of multiple proteins, with or without other biomolecules or ligands bound. Characterization of protein complexes/assemblies, including identification of all binding partners, their relative architecture/topology in the complex, conformational changes upon binding and the relative binding affinities of partners is key to developing a better understanding of how these complex systems carry out their normal biological functions and how alterations of architecture can lead to malfunction. MS is emerging as a powerful tool for structural biology, with the combination of multiple MS approaches enabling the structural characterization of biomacromolecules. However, development of both MS instrumentation and methods is necessary to fully implement the use of MS in routine, reliable, and rapid structural characterization studies. To advance the technological development of native MS for structural biology applications and to illustrate how native MS can guide and integrate with other structural biology approaches, we have identified three main classes of protein complexes for which significant technological challenges exist, compelling PIs to use multiple structural biology approaches. These are 1) protein:protein, 2) membrane protein and membrane protein:lipid complexes, and 3) RNA:protein, complexes. The DBPs were selected to encompass projects with high biomedical significance where progress depends on solving substantial technical challenges. These projects will benefit significantly from improved native MS workflows. Solving their structural challenges, in the context of other structural tools that they use, will also provide solutions and guidance that are applicable to a much broader spectrum of researchers. Effective communication is key to the progress of the DBPs, so that the Resource fully understands the nature of the biological problem being addressed and so that the collaborating investigators fully understand the current capabilities of each of the technologies. Initial project meetings have been held for each of the DBPs and preliminary data have been obtained. Regular meetings will be held to assess the progress and plan future experiments. DBP investigators and their groups will be encouraged to present the work at conferences they attend, with an appropriate acknowledgement of the nMSSB Resource. A DBP will be considered successfully completed when it has reached a point where multiple high-quality manuscripts are prepared and published, the DBP’s questions can be answered with technology existing at that stage, and the DBP is no longer driving the Resource to improve the native MS technology. The Resource will be involved with the authoring and preparation of each of the relevant joint manuscripts. For publication, journals will be targeted that have high-impact and are read by the broad community, which aids in our dissemination plan of bringing the technology to a broad audience, including structural biologists and biomedical researchers.