Recent science highlights from the ALS-ENABLE beamlines

ALS-ENABLE scientist contributes to Cell publication on SARS-CoV-2 spike protein

ALS-ENABLE scientist, Jay Nix at the MBC beamline 4.2.2 participated in the structure solution for a recently published paper in Cell, Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

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Structural biology in the spotlight

ALS Enable scientist helps to determine the atomic structure of a coronavirus protein

Using X-ray crystallography at beamline 5.0.2, Marc Allaire, helped to build an atomic model of ORF8, laying the groundwork for other groups to study the protein in more detail.

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               Nasal spray prototype

Helping to stop the rise of SARS-CoV-2

Scientists at ALS Enable contribute to groundbreaking research that may help to stop the rise of SARS-CoV-2 infections that have had devastating effect on our health and economy worldwide. In the article (currently in preprint) the authors describe the development of single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. This discovery may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century.

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Guiding the design of COVID-19 vaccines and therapeutics

ALS Enable scientists contribute to an article published in CELL (volume 183, issue 4, November 12, 2020) in which the authors describe the analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection. This discovery is a crucial part of understanding immune protection and identifying targets for vaccine design.

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Fighting bacterial infections

How Proteins Remodel DNA in Bacteria under Stress

ALS-ENABLE beamlines use multiscale, multimodal visualization techniques to clarify how proteins remodel bacterial DNA in response to stressful environments. At the mesoscale, small-angle x-ray scattering (SAXS) at Beamline 12.3.1 made it possible to determine the overall shapes of HU–DNA complexes in solution. At the nanoscale, protein crystallography at Beamline 8.3.1 allowed identification of the molecular-level mechanisms that mediate DNA bundling.

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X-ray Experiments zero in on COVID-19 Antibodies

With help from ALS-ENABLE beamline 5.0.2, an international scienctific team has identified an antibody that neutralizes the COVID-19-causing coronavirus. In a paper published in Nature, the scientists note that the antibody is already moving toward clinical trials.

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Assembly Lines for Designer Bioactive Compounds

Researchers successfully bioengineered changes to the molecular “assembly line” for bioactive compounds, based in part on insights gained from Small-Angle X-ray Scattering (SAXS) data collected at SIBYLS beamline 12.3.1.

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Characterizing the forces that hold membrane proteins together

Designed membrane proteins are used to better understand the competing forces that stabilize this category of protein.

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Designer proteins that fit together like DNA

Proteins designed to mimic the structure of DNA can be used as building blocks for self-assembling protein machines.

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Toward defeating influenza

Structures of several influenza antiviral drug molecules bound to their targets in both open and closed conformations provide an atomic-level blueprint from which to design more effective anti-influenza drugs that can overcome growing drug resistance.

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Designing a protein to capture small molecules

For the first time, scientists have created, entirely from scratch, a protein capable of binding to a small target molecule.

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Decoding a Calcium dependent switch

Certain voltage-gated proteins in cell membranes are responsible for controlling the flow of ions across the membrane and thus are important in electrical activity in the heart and brain. This study using both diffraction and scattering beamlines of ALS-ENABLE revealed the role of calcium in the regulation of a class of these important proteins.

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How antidepressants block serotonin transport

Serotonin is a diminutive and deceptively simple-looking neurotransmitter molecule, yet a very complex “machinery” is required for neurotransmitter recognition, transmission, and recycling. The malfunctioning of this protein machinery can cause conditions such as depression, obsessive-compulsive disorder, aggression, anxiety, and Parkinson’s disease. In addition, drugs of addiction, such as methamphetamines, act on this system, causing serious damage and profoundly affecting the well-being of individuals. At the ALS, researchers were able to obtain x-ray crystallographic structures of the difficult-to-crystallize human serotonin transporter bound to two commonly prescribed antidepressant drug molecules. The resulting details about the transporter structure and mechanism will help in the design of new, more effective therapeutics for treating depression and anxiety.

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Behind the new gene-editing tool

The CRISPR-Cas system has recently transformed the way that scientists are able to perform gene editing, making it much easier and more accurate than ever before. In this study, the structures of the system with DNA substrates revealed just how specific DNA code is located with such specificity.

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