Structural Cell Biology Core

University Of Calif-Lawrenc Berkeley Lab, Berkeley CA

Investigators

Linked publications & trials

Abstract

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