Science Highlights

How Proteins Remodel DNA in Bacteria under Stress

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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Two recent papers from Doudna and Marletta groups combine SAXS with Cryo-EM

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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Designing and defining dynamic protein cage nanoassemblies in solution

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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Formation of repressive complex in the mammalian circadian clock is demoted by the secondary pocket of CRY1

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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Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor

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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SAXS used to elucidate mechanism of inner-ear mechanotransduction

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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Exploring the Repeat Protein Universe through Computational Protein Design

The facilities and staff at the SYBILS beamline contributed to this breakthrough study exploring the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Naturally occurring proteins–chains of amino acids that fold into functional, three-dimensional shapes–are believed to represent just a small fraction of the universe of…
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Structural Basis for Marburg Virus Neutralization by a Cross-Reactive Human Antibody

The facilities and staff at the SIBYLS beamline contributed to this recent structural study of a human antibody that is able to neutralize Marburg and Ebola viruses. >The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ…
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