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）SBDR的主要挑战来自动态和 参与DNA修复过程的大蛋白质复合物的协调组装。这些复合物 经历功能上重要的构象变化和修饰。SCB核心将提供 适用于SBDR项目和计划的结构专业知识和技术目标是，创建一个功能桥梁 在原子分辨率结构和分子包络之间，并帮助关闭静态晶体之间的差距 结构和生物相关的多组分高分子机器。特别是，SCB核心 将为SBDR提供三种不同的结构分析方法。(1)多波长 单晶X射线衍射将提供离散态的高分辨率结构。(2)小 角X射线散射（SAXS）将通过可视化表征蛋白质复合物的溶液动力学， 柔性区域和诱导的构象变化。(3)扫描力显微镜（SFM） 分子，可通过怀曼实验室，将提供有关DNA和蛋白质动力学的信息， 将揭示以前无法使用晶体学或 SAXS技术。SCB核心旨在为SBDR项目提供必要的工具， 熟练克服结构生物学的挑战固有的大型复杂的分析。的 申请的资金为工作人员提供了最大限度地与EMB核心互动的机会，并为SBDR使用 先进光源（ALS）的生命科学结构集成生物学（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 这是一个为单晶X射线衍射和SAXS提供可调波长的资源。在scb 核心将开发软件，解决目前在DNA修复蛋白分析中的局限性，包括 该软件将通过系统和 X射线晶体结构与EM和SAXS产生的分子包层的客观拟合 实验SCB核心将测试，开发和提供先进的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 修复将产生对多组分系统的深入了解，这些系统通过对以下方面的研究仍然是难以捉摸的： 单独组成的生物分子。SCB核心的结果将被应用于理解 通过与UCSF的相互作用，研究癌症病因学和潜在的癌症诊断和治疗学 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.