SIBYLS is excited to announce we have a biochemist postdoc fellow opening. This is a great opportunity to work with experienced and innovative scientists in the field of structural biology. We are looking for someone who wants to develop and apply biology for multi-component biological macromolecules. You will be a part of a team that designs, develops, and applies synchrotron methods to characterize macromolecules and the assemblies they form. On top of all that, you will get an amazing, ever-changing view of the Bay, San Francisco skyline, and both the Golden Gate bridge and Bay bridges! For more information and to apply go here.
The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined biophysical approaches to gain insights into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. Structurally-guided mutational analyses based on the crystal structure of the human BRCT-BRCT heterodimer identified the network of salt bridges that together with the N-terminal extension of the XRCC1 C-terminal BRCT domain constitute the XL molecular interface. Coupling size exclusion chromatography with small angle X-ray scattering and multiangle light scattering (SEC-SAXS-MALS), we determined that the XL is more compact than either XRCC1 or LigIIIα, both of which form transient homodimers and are highly disordered. The reduced disorder and flexibility allowed us to build models of XL particles visualized by negative stain electron microscopy that predict close spatial organization between the LigIIIα catalytic core and both BRCT domains of XRCC1. Together our results identify an atypical BRCT-BRCT interaction as the stable nucleating core of the XL that links the flexible nick sensing and catalytic domains of LigIIIα to other protein partners of the flexible XRCC1 scaffold.
Read more about it here.
In the Snell group’s (HWI) recent paper, Dr. Tim Stachowski led a research effort entitled “SAXS studies of X-ray induced disulfide bond damage: Engineering high-resolution insight from a low-resolution technique.” This work combined a protein engineering approach with SAXS to monitor cleavage of a specific bond from exposure to the X-ray beam. X-ray induced disulfide bond breakage is a common phenomenon in X-ray crystallography but there is limited information on how susceptible disulfides are to low X-ray doses and in solution. To detect disulfide bond breakage with a low-resolution technique like SAXS, a protein was coerced to dimerize through a susceptible disulfide bond. During X-ray exposure, breakage of the bond was apparent by monitoring how the protein sample transitioned from a dimer to a monomer using several metrics calculated directly from the SAXS data. These findings are an important step towards understanding if a connection can be made between the detailed crystallographic radiation damage mechanisms and the solution state, which is closer to physiology, as well as understanding how samples can potentially be altered during the course of SAXS experiments.
SIBYLS beamline scientists contribute to the discovery of an ancient form of rubisco, the most abundant enzyme on earth and critical to life as we know it. By analyzing SEC-SAXS data collected at beamline 12.3.1, they were able to capture how the enzyme’s structure changes during different states of activity. Read all about it here.
Even though we had to hold our BioSAXS workshop virtually this year, it turned out to be one of our best ever. We had more 60 participants over the two day workshop, zooming in from all over the US and parts of Europe! Keep checking for more workshops in the future. We offer monthly (sometimes even more frequent) “office hours” as well. For more information go to ALS-ENABLE.
SIBYLS will host our 11th annual BioSAXS workshop during the Advanced Light Source 2020 User Meeting which will be held Tuesday, August 25 - Friday, August 28. For the first time, it will be held VIRTUALLY.
This workshop is designed for current and future SIBYLS and ALS-ENABLE users. We will provide participants with software tutorial sessions for biological SAXS and crystallography. The latest advances in SAXS studies on biological systems will be discussed with particular focus on advances in our mail-in SAXS program and integrating bioSAXS analysis. SIBYLS Lab’s SAXS Beamline Scientists will introduce the future of high throughput and size exclusion coupled SAXS (HT-SAXS and SEC-SAXS). We will present talks about integrating high-resolution models in the SAXS modeling. Introductory crystallography will also be discussed. We will provide an opportunity for participants to present and discuss their projects with the SIBYLS and ALS-ENABLE staff. Interested users will present their case studies for workshop analysis. This will provide for a flux of ideas among workshop participants, and inspire new perspectives for future data analysis.
Click on the link below for the most recent schedule :
2020 BioSAXS workshop Schedule DAY 2.pdf
Registration is now open. It’s Free! To attend the workshop you need to REGISTER for the 2020 ALS user meeting. When you register, indicate that you plan to attend the “Macromolecular Structural Biology at the ALS” workshop.
Inquires : Kathryn Burnett
SIBYLS beamline 12.3.1 is one of a limited number of beamlines at the ALS that has been given approval to operate. We are offering HT-SAXS and SEC-SAXS to support academic and industry groups pursuing structural biology on all research, including on the key protein components of the coronavirus that causes COVID-19. To book a beamtime slot go to our SIBYLS Mail-in website.
Inquires: Contact Kathryn Burnett or Greg Hura
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. In this view, the protein particles E, S, and M, also located on the outer surface of the particle, have all been labeled as well. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19).
Quick Links
