SIBYLS scientist, Michal Hammel, analyzing data collected at the SIBYLS beamline gained insight into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. This ligase complex is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination.…
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In this top 10 cited article using HT-SAXS data collected at SIBYLS, Chris Brosey, along with John Tainer, describe the value and versatility of Small Angle X-ray Scattering. The authors discuss evolving SAXS theory, methods, and applications that extend the field of small-angle scattering beyond simple shape characterization. From capturing architecture and dynamics to enabling…
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By analyzing SAXS data collected at BL 12.3.1, SIBYLS scientists were able to determine the overall shapes of HU-DNA complexes in solution, helping to clarify how proteins remodel bacterial DNA in response to stressful environments. This discovery, enabled by three beamlines at the Advance Light Source, could lead to new strategies for controlling microbial behavior…
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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…
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Central challenges in the design of large and dynamic macromolecular assemblies for synthetic biology lie in developing effective methods for testing design strategies and their outcomes, including comprehensive assessments of solution behavior. The authors of this paper created and validated an advanced design of a 600-kDa protein homododecamer that self-assembles into a symmetric tetrahedral cage.…
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In this paper, the authors show that CRY1, a protein coding gene that activates circadian gene expression and metabolic states and circadian oscillators, binds directly to the PAS domain core of CLOCK:BMAL1. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24 hr periodicity of gene expression. Integrative modeling and solution X-ray scattering…
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Apoptosis-inducing factor (AIF) is critical for mitochondrial respiratory complex biogenesis and for mediating necroptotic parthanatos; these functions are seemingly regulated by enigmatic allosteric switching driven by NADH charge-transfer complex (CTC) formation. In this paper the authors define molecular pathways linking AIF’s active site to allosteric switching regions by characterizing dimer-permissive mutants using small-angle X-ray scattering…
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Tip link filaments convey force and gate inner-ear hair-cell transduction channels to mediate perception of sound and head movements. Cadherin-23 and protocadherin-15 form tip links through a calcium-dependent interaction of their extracellular domains made of multiple extracellular cadherin (EC) repeats. These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved…
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