Scientists from three national laboratories who specialize in revealing the atomic structure of proteins collaborated to model the complex protein responsible for SARS-CoV-2 replication, revealing potential weak spots for drug development.
Papain-like protease (PLpro) from SARS-CoV-2 plays essential roles in the replication cycle of the virus that is the cause of the global COVID-19 pandemic. In human cells that the virus has infected, PLpro seeks out and binds with the interferon-stimulated gene 15 (ISG15) protein, a key component of the cells’ immune response. PLpro strips ISG15 from other cellular proteins to aid SARS-CoV-2 in evading the body’s immune system.
Scientists at Oak Ridge National Laboratory (ORNL) used small-angle neutron scattering (SANS) at the High Flux Isotope Reactor (HFIR) combined with computational techniques to reveal the molecular details of how the two proteins interact. Susan Tsutakawa, a staff scientist in the Molecular Biophysics and Integrated Bioimaging (MBIB) Division, obtained small-angle x-ray scattering (SAXS) data on the PLpro-ISG15 complex at Berkeley Lab’s Advanced Light Source (ALS) to augment the SANS work.
In a study appearing in Nature Plants, researchers from UC Davis, UC Berkeley, and Berkeley Lab report the discovery and characterization of a previously undescribed lineage of form I rubisco – one that the researchers suspect diverged from form I rubisco prior to the evolution of cyanobacteria. The novel lineage, called form I’ rubisco, gives researchers new insights into the structural evolution of form I rubisco, potentially providing clues as to how this enzyme changed the planet.
The work was led by Patrick Shih, a UC Davis assistant professor and the director of Plant Biosystems Design at the Joint BioEnergy Institute (JBEI), and Doug Banda, a postdoctoral scholar in his lab.
Biosciences Area researchers and their collaborators have determined how a protein called XPG binds to and reshapes damaged DNA, illuminating its role in averting genetic disease and cancer.
Atomic-scale structural analyses performed at Berkeley Lab’s Advanced Light Source (ALS) are helping scientists understand the inner workings of the enzyme “assembly lines” that microbes use to produce an important class of compounds, many of which have uses as antibiotics, antifungals, and immunosuppressants.
These cellular machines, known as nonribosomal peptide synthetases (NRPSs), are large, multi-enzyme clusters that synthesize compounds by passing a precursor molecule from one module to the next, with each “station” catalyzing a change in the molecule. In the past decade, researchers have learned a great deal about how individual NRPS modules work, but an understanding of how the assembly lines function as a whole has been lacking. In the hopes of eventually engineering custom NRPSs to make new and improved medicines, a team led by McGill University began investigating the bacterial NRPS that synthesizes the antibiotic gramicidin.