SCVD Faculty

Michael B Sherman, PhD

Michael B Sherman, PhDMy major interests are in three-dimensional organization of large macromolecular complexes and cell organelles by cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). CryoEM allows to study symmetric particles, e.g. spherical viruses, ordered assemblies (2D crystals, helical arrays, etc.) and asymmetrical complexes in their native state. Unique structures are studied using cryoET. I am interested in structural studies of symmetrical as well as of asymmetrical particles by these techniques. Spherical viruses are highly symmetrical, they infect variety of animal and plant cells. The structure opens way to understand their mechanism of action and allows to target specific epitopes to neutralize them. We have constructed first-of-its-kind BSL-3 cryo-EM containment facility at UTMB where I have collected images of Western equine encephalitis virus (WEEV), a biological safety level 3 (BSL-3) agent. This is the first case of safe imaging of a BSL-3 agent in cryoEM. These images were used to determine the three-dimensional structure of this important human pathogen at 1.3 nm resolution. Asymmetrical assemblies are the most challenging case for structural studies. An example is LDL, one of the major lipid carriers in blood. They have only one protein component, apolipoprotein B-100, whereas the rest of the particle (78%) is composed of various lipids. Amazingly, despite their high lipid content, they are rigid enough to maintain their overall shape and characteristic lamellar organization of the core. We found that the lamellae most likely consist of cholesteryl esters; therefore with low or no cholesterol in LDL they do not have striated cores and are less rigid. The findings provide an important hypothesis that LDL depending on cholesterol content would interact with LDL receptors differently causing lipid metabolic disorders.

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