The cover feature shows a chessboard (representative of KRAS mutant cells) and how the concerted action of the MEK inhibitor cobimetinib (rook) and the new selective pan-RAF inhibitor GNE-0749 (queen) force the opposing king (phospho-ERK, the downstream signaling node of RAF and MEK) into checkmate. Read more »
Mystery Protein Helps COVID–19 Avoid Immunity
Using the Advanced Light Source (ALS), researchers solved the structure of ORF8, a protein specific to SARS-CoV-2. Understanding the structure of ORF8 opens the door to therapy studies targeting SARS-CoV-2, the virus responsible for causing COVID-19. Read more »
To Speed Discovery, Infrared Microscopy Goes “Off the Grid”
Researchers developed a highly efficient way to collect infrared microscopy data that avoids the use of slow, grid-based raster scans. The method substantially reduces image-acquisition times by autonomously increasing sampling density in regions of interest, facilitating infrared spectromicroscopy of biochemical processes in real time. Read more »
3D Whole-Cell Mapping of Insulin Secretion
Researchers used soft x-ray tomography to gain a 3D whole-cell view of how insulin-producing pancreatic cells react upon exposure to glucose and a diabetes drug. The approach enables direct quantification of intracellular responses before, during, and after cell stimulation, providing new insights into how drugs alter cell function. Read more »
Construction, characterization and crystal structure of a fluorescent single-chain Fv chimera
In vitro display technologies based on phage and yeast have a successful history of selecting single-chain variable fragment (scFv) antibodies against various targets. However, single-chain antibodies are often unstable and poorly expressed. We explore the feasibility of converting scFv antibodies to an intrinsically fluorescent format by inserting a monomeric, stable fluorescent protein between the light- and heavy-chain variable regions. Read more »
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells
A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009, that targets acute myeloid leukemia blasts and leukemia stem cells. Read more »
Newly Discovered Photosynthesis Enzyme Yields Evolutionary Clues
Scientists have discovered a primitive form of rubisco, a photosynthesis enzyme that has helped shape life on Earth. Detailed information about its structure, determined using complementary techniques at the ALS, will help scientists understand how carbon-fixing organisms oxygenated the atmosphere and how modern plants evolved. Read more »
Jennifer Doudna and the Nobel Prize: The Advanced Light Source Perspective
The 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmanuelle Charpentier for the development of a world-changing gene-editing technology. At the ALS, Doudna’s work on CRISPR-Cas9 was enabled by many visionary people with innovative ideas, implemented in support of a world-class structural biology program. Read more »
Study Finds ‘Missing Link’ in the Evolutionary History of Carbon-Fixing Protein Rubisco
Scientists discovered an ancient form of rubisco, the most abundant enzyme on Earth and critical to life as we know it. Found in previously unknown environmental microbes, the newly identified rubisco provides insight into the evolution of the photosynthetic organisms that underlie the planet’s food chains. Read more »
Providing New Technologies for Vaccine Development
Antigens can sometimes be attached to a protein scaffold to mimic the shape of a virus and elicit a stronger immune response. Scientists developed a method to design such proteins, and ALS data helped to visualize the atomic structure and determine the dynamics of the designed scaffolds. Read more »
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