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).
Unfortunately, because of the coronavirus outbreak, we will not be holding the SAXS workshop in person on April 2nd. We will instead hold a virtual meeting. In the meantime, Greg Hura will be holding shorter zoom meetings every two weeks (or so) to go over preliminary processing of HT-SAXS and Michal Hammel will run zoom meetings to go over SEC-SAXS data processing.
If you are interested in joining a zoom meeting, please email Kathryn Burnett.
The Doudna group, explained in their recent paper, “Structural basis for AcrVA4 inhibition of specific CRISPR-Cas12a” combine SAXS with Cryo-Em to show the C-terminal binding domain is sufficient for Cas12a inhibition. CRISPR-Cas systems provide bacteria and archaea with programmable immunity against mobile genetic elements. Evolutionary pressure by CRISPR-Cas has driven bacteriophage to evolve small protein inhibitors, anti-CRISPRs (Acrs), that block Cas enzyme function by wide-ranging mechanisms. The inhibitor AcrVA4 uses a previously undescribed strategy to recognize the L. bacterium Cas12a (LbCas12a) pre-crRNA processing nuclease, forming a Cas12a dimer, and allosterically inhibiting DNA binding. Their findings explain a new mode of CRISPR-Cas inhibition and illustrate how structural variability in Cas effectors can drive opportunistic co-evolution of inhibitors by bacteriophage.
In the Marletta group’s recent paper, “Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy” they corroborate the structural elongation of the particle observed in cryo-EM using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO. Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. They determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains.
Date: October 2 - 3, 2019 Location: Building 33 at Lawrence Berkeley National Laboratory, Berkeley, CA
Building / ROOM : 33-306
This two-day workshop will cover frontiers in biological SAXS and will provide participants with software tutorial sessions for biological SAXS in addition to hands-on training in experimental techniques. The latest advances in SAXS studies on biological systems will be discussed with a particular focus on dynamic and flexible structures in biomolecules, membrane protein scattering, and complementary methods in crystals and in solution. Updates on current developments of software for SAXS analysis and solution structure modeling will be illustrated.
The first day of the workshop will begin with a brief run-through on current updates. Greg Hura and Michal Hammel, Berkeley Lab’s SAXS beamline scientists, will introduce the capabilities of the mail-in program at SIBYLS and the future of high-throughput and SEC-SAXSat the SIBYLS Beamline. Distinguished speakers will contribute to the basis of the workshop over the two days by sharing complementary experimental approaches and modeling techniques. This will provide for a flux of ideas among workshop participants and inspire new perspectives for future data analysis. The second day will be dedicated to practical hands-on exercises with experts in SAXS software for data processing (SCATTER, FrameSlice and RAW, SAXS similarity maps, modeling tools (FOXS - MultiFoXS, BILBOMD and SAXS shape calculator).
Enrollment is limited to 30 participants.
Inquires: Kathryn Burnett
Registration: Registration is now open. To attend the workshop you need to REGISTER for the 2019 ALS user meeting. When you register, indicate that you plan to attend the “10th Annual SIBYLS bioSAXS Workshop”.
SCHEDULE : October 2nd, 2019
Building / ROOM : 33-306
Day 1: BioSAXS Workflow
8:30-8:40 Introduction to the SIBYLS team and Workshop Agenda (Hammel)
8:40 - 9:20 Key Note - Mark Glover (Uni. Alberta) Building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time
9:20 - 10 SAXS basics (G. Hura)
10 - 10:20 Break
10:20 - 12:20pm HT-SAXS, details of collection, getting intensity vs q (Burnett and Hura)
12:20 - 1:30 Lunch
1:30 - 2:30 SEC-SAXS-MALS, details of collection, getting intensity vs q (Hammel and Rosenberg)
2:30 - 3:00 ALS and beamline tour (SIBYLS team)
3:00 - 3:30 Analysis of SEC-SAXS-MALS (Hammel)
3:30- 3:50 Break
3:50 - 4:10 Ben Horst ( UC Berkeley) Allosteric activation of the NO receptor soluble guanylate cyclase revealed by cryo-EM and SAXS
4:10 - 4:30 Lauren Carter (University of Washington) De novo protein design validated by SAXS
4:30 - 4:45 Soumya Remesh (NCI) Functional Relevance of Interleukin-1 Receptor Inter-domain Flexibility for Cytokine Binding and Signaling
4:45 - 5 Curtis Hodge (LBNL) Functionalized Nanocage for Antibody Display
October 3rd, 2019 Day 2: Beyond Shapes with SAXS
8:30 - 9:15 HT-SAXS examples (Hura)
9:20 - 10 Special SEC-SAXS-MALS tools with RAW and Evolving SVD (Hammel)
10 - 10:20 Break
10:20 - 12:20pm User posed problem
12:20 - 1:30 Lunch
1:30 -2:00 SAXS modeling, BILBOMD, FoXS etc… (Hammel)
2:00-5:00 Hands on practical
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