Structural Cell Biology Core

结构细胞生物学(SCB)核心为结构细胞提供关键技术和支持 DNA修复机器生物学(SBDR)计划。SBDR的主要挑战来自动态和 参与DNA修复过程的大型蛋白质复合体的协调组装。这些复合体 经历功能上重要的构象变化和修饰。渣打银行核心将提供 适合SBDR项目和计划目标的结构专业知识和技术，创建功能桥梁 原子分辨结构和分子包络之间的关系，并有助于缩小静态晶体之间的差距 结构和生物相关的多组分大分子机器。特别是，SCB核心 将为SBDR提供三种截然不同和互补的结构分析方法。(1)多波长 单晶X射线衍射将提供高分辨率的分立态结构。(2)小规模 角X射线散射(SAXS)将通过可视化的方式表征蛋白质络合物的溶液动力学 灵活的区域和诱导的构象变化。(3)扫描力显微镜(SFM) 怀曼实验室提供的分子将提供有关DNA和蛋白质动力学的信息，以及 将揭示以前无法使用结晶学或 SAXS技术。SCB核心旨在为SBDR项目提供必要的工具和 熟练地克服大型复合体分析所固有的结构生物学挑战。这个 申请的资金提供工作人员，以最大限度地与教统局核心互动，并供SBDR使用 高级光源(ALS)上的结构集成生命科学生物学(SIBYLS)光束线 劳伦斯伯克利国家实验室(LBNL)。SIBYLS光束线是一种独特的同步加速器 为单晶X射线衍射和SAXS提供可调波长的资源。渣打银行 CORE将开发软件，解决目前DNA修复蛋白分析中的限制，包括 软件将结合高分辨率和低分辨率技术的结果，通过系统和 X射线晶体结构在EM和SAXS分子包层中的客观拟合 实验。SCB Core将测试、开发并提供高级工具来检测和测量翻译后 修改。理解DNA大分子机器的动态结构 修复将产生对多组件系统的洞察，这些系统通过研究 单组分生物分子。来自SCB核心的结果将应用于理解 通过与加州大学旧金山分校的互动，癌症病因学和潜在的癌症诊断和预后 综合癌症中心。

The Structural Cell Biology (SCB) Core provides critical technologies and support for the Structural Cell Biology of DNA Repair Machines (SBDR) Program. Major challenges of SBDR stem from the dynamic and coordinated assembly of large protein complexes involved in DNA repair processes. These complexes undergo functionally important conformational changes and modifications. The SCB Core will provide structural expertise and technologies suitable for SBDR project and program Aims, create a functional bridge between atomic resolution structures and molecular envelopes, and help close the gap between static crystal structures and biologically relevant, multi-component macromolecular machines. In particular, the SCB Core will provide SBDR with three distinct and complementary methods for structural analyses. (1) Multiwavelength single crystal X-ray diffraction will provide high-resolution structures of discrete states. (2) Small Angle X-ray Scattering (SAXS) will characterize the solution dynamics of protein complexes by visualizing flexible regions and induced conformational changes. (3) Scanning Force Microscopy (SFM) of single molecules, available through the Wyman lab, will provide information about DNA and protein dynamics, and will reveal structural insight into heterogeneous mixtures previously inaccessible using crystallographic or SAXS techniques. The SCB Core is designed to supply the SBDR projects with the necessary tools and proficiency to overcome the structural biology challenges inherent to analysis of large complexes. The requested funding provides staff to maximize interaction with the EMB Core and for SBDR use of the Structurally Integrated Biology for Life Sciences (SIBYLS) beamline at the Advanced Light Source (ALS) at the Lawrence Berkeley National Laboratories (LBNL). The SIBYLS beamline is a unique synchrotron resource that provides tunable wavelengths for both single crystal X-ray diffraction and SAXS. The SCB Core will develop software that addresses current limitations in the analysis of DNA repair proteins including software that will combine results from high and low resolution techniques through the systematic and objective fitting of X-ray crystal structures into molecular envelopes generated by EM and SAXS experiments. The SCB Core will test, develop, and provide advanced tools to detect and measure posttranslational modifications. Understanding the dynamic structures of macromolecular machines for DNA repair will generate insights into multi-component systems that have remained elusive through the study of individual component biomolecules. The results from the SCB Core will be applied to the understanding of cancer etiology and potential cancer diagnostics and prognostics through interactions with the UCSF Comprehensive Cancer Center.