On March 31, a small team of staff at Berkeley Lab’s Advanced Light Source (ALS), which produces beams of X-rays and other types of light to support a wide variety of experiments for researchers around the world, launched several COVID-19-related experiments for other scientists who controlled the work remotely. X-rays allow researchers to map out the 3D structure of proteins relevant to diseases at the scale of molecules and atoms. Structural studies can lead to drugs that target and attack the virus while leaving other vital systems intact, for example, or that can otherwise improve the body’s defenses against the virus.
Seeking to develop a direct inhibitor of a mutant protein caused by errors in the KRAS gene, researchers at Amgen conducted X-ray crystallography of KRAS(G12C) proteins using the Berkeley Center for Structural Biology (BCSB) beamlines at the Advanced Light Source (ALS). The high-resolution structural maps generated from the data acquired revealed a small pocket on the molecule. Now, an investigational cancer drug that binds in this pocket will be evaluated in phase 2 clinical trials.
Berkeley Center for Structural Biology (BCSB) beamlines 5.0.2, 8.2.1, and 8.2.2 at the Advanced Light Source (ALS) were used to experimentally verify de novo protein structures designed by citizen scientists playing the computer game Foldit.
The crystallographic study of STING (stimulator of interferon genes), a transmembrane protein that plays a key role in innate immunity, in complex with TBK1 (serine/threonine-protein kinase), an enzyme that regulates the inflammatory response to foreign DNA, is extremely challenging due to weakly diffracting crystals. But thanks to the expertise of Berkeley Center for Structural Biology (BCSB) scientists, researchers from Texas A&M University (TAMU) were able to pinpoint the conserved motif of STING that mediates the recruitment and activation of TBK1. They published their results in Nature.
To better understand how coronavirus antibodies work, a team of researchers at the University of Washington studied spike protein structures in complex with neutralizing antibody fragments isolated from SARS and MERS survivors. To visualize how the spike structures interact with the antibody fragments, they used a cryo-electron microscopy (cryo-EM) for the spikes, which are resistant to crystallization, and protein crystallography for the fragments. The high-resolution x-ray crystallography was performed at the Advanced Light Source (ALS) Beamline 5.0.1, part of the Berkeley Center for Structural Biology (BCSB).