A highly sensitive lateral flow assay—the same type of device used in home pregnancy tests—could be developed using pairs of rigid antibodies that bind to the SARS-CoV-2 nucleocapsid protein. SAXS data showed that a particular pair of monoclonal antibodies bound to the nucleocapsid protein very strongly and stably, in part due to the antibodies’ rigidity. Read more »
Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology
LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Read more »
Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor
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 »
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 »
A Detailed Look Inside Tsetse Flies
To better understand the unique reproductive biology of tsetse flies, which are carriers of the parasites that cause a deadly infection known as African sleeping sickness, researchers explored the intact organs and tissues of tsetse flies using a powerful 3D x-ray imaging technique at Berkeley Lab’s Advanced Light Source. Read more »
Inhalable COVID-19 Protection via Synthetic Nanobodies
Protein structures obtained in part at the ALS helped researchers to increase the potency of simplified antibodies (nanobodies) designed to neutralize SARS-CoV-2. Stable enough to be used in inhalers or nasal sprays, the nanobodies offer a new option, aside from injected vaccines, for COVID-19 prevention and treatment. Read more »
Xylella fastidiosa causes transcriptional shifts that precede tylose formation and starch depletion in xylem
During Pierce’s disease, Xylella fastidiosa triggers transcriptional changes in grapevines and induces major physiological responses, including tylose formation and starch depletion. X-ray computed microtomography and a machine-learning algorithm were used to track the depletion of starch reserves in the xylem of a grapevine stem infected with Pierce’s disease. Read more »
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