Show-Me State Times

Low-density lipoproteins (LDL), often referred to as bad cholesterol, have been identified as a significant factor in heart disease. However, the intricacies of their function have remained elusive until recently. Researchers at the University of Missouri have now unveiled the specific shape and structure of ApoB100, a crucial protein that encases LDL particles, enabling their movement through the bloodstream.

This breakthrough could pave the way for developing new drugs targeting LDL, offering more precise treatments for high cholesterol and heart disease while potentially minimizing side effects associated with medications like statins.

Zachary Berndsen and Keith Cassidy were brought to Mizzou due to their expertise in cryo-electron microscopy, which uses electrons to map out the 3D structure of biological molecules. Their research was facilitated by investments in infrastructure at Mizzou's Electron Microscopy Core at the Roy Blunt NextGen Precision Health building.

“These cryo-electron microscopes allow us to see things at a much higher resolution than traditional microscopes,” said Berndsen, an assistant professor in the MU School of Medicine. He emphasized that this technology enables scientists to observe individual proteins' shapes, significantly smaller than typical cells.

After Berndsen utilized a large cryo-electron microscope to discern ApoB100's structure, Cassidy employed artificial intelligence alongside Mizzou’s supercomputers named Hellbender to refine this understanding further. “By integrating an AI neural network called AlphaFold with the cryo-electron microscopy images, we were able to get an even more detailed and higher-resolution picture of the structure of ApoB100,” said Cassidy, an assistant professor of biological physics.

The discovery not only enhances comprehension of fat and cholesterol metabolism but may also lead to improved testing and treatment for "bad" cholesterol. Berndsen highlighted that current cholesterol testing methods lack specificity and suggested that measuring ApoB100 levels could provide a more accurate risk assessment for heart disease.

Both researchers have personal connections to heart disease within their families. “We are trying to bridge the gap between the basic science we are doing now and the applied health benefits down the road,” Berndsen stated.