The Todd Yeates laboratory in the UCLA Department of Chemistry & Biochemistry studies supra-molecular protein assemblies. Recent investigations from the Yeates lab have focused on the characterization of organelle-like structures known as bacterial microcompartments, comprised of a protein shell encapsulating enzymes and other proteins. The lab has successfully applied X-ray crystallography to reveal the structure of a novel 13 nm dodecahedral nanocage assembled from a redesigned bacterial microcompartment shell protein. Viruses, including SARS-CoV-2 that causes COVID-19, have their genetic material enclosed within three-dimensional viral capsids. Because bacterial microcompartments are reminiscent of viral capsids, efforts to structurally characterize these systems will shed light on three-dimensional characteristics of SARS-CoV-2.
The SARS-CoV-2 capsid functions to protect the nucleic acid from enzyme digestion, attaches the virion to a host cell via specific sites on its surface, provides proteins that allow the virus to penetrate the host cell membrane, and is often used to inject viral genetic material into the host cell’s cytoplasm. X-ray crystallography studies of SARS-CoV-2 virus will provide insight towards how this virus interfaces with host cells, allowing for the design of novel therapeutics preventing such interactions.
Additional techniques developed by the Yeates lab can be applied to the study the SARS-CoV-2 viral capsid, and ultimately drive further understanding of COVID-19 disease pathogenesis. Previously, researchers in the Yeates lab have modeled the transport of selective metabolites across the propanediol bacterial microcompartment shell. Similar molecular dynamics simulation studies may be used to analyze small-molecule transport across a the SARS-CoV-2 shell.
Link to Faculty website: https://yeateslab.mbi.ucla.edu/
Link to relevant cases:
1) Molecular Dynamics Simulations of Selective Metabolite Transport across the Propanediol Bacterial Microcompartment Shell. J Phys Chem B. (2017)
2) Structure of a novel 13 nm dodecahedral nanocage assembled from a redesigned bacterial microcompartment shell protein. Chem Commun (Camb). (2016)