Cholesterol has long been implicated in diverse aspects of human health and disease. It is an important structural component for animal cell membrane, and serves as precursors for the biosynthesis of vitamin D, bile acids and steroid hormones. Besides, cholesterol has also been found to play a critical role in signaling pathways. Whereas, the high cholesterol level is associated with elevated risk for many diseases, such as atherosclerosis, coronary heart disease, stroke, high blood pressure and diabetes. As cholesterol is both vital and lethal, ensuring its homeostasis is important for maintaining health. Cellular cholesterol homeostasis is among the most intensely regulated processes in biology and is tightly regulated at multiple levels. This seminar will explore the structural and mechanistic insights into the cholesterol-related proteins, mainly focusing on two sterol-sensing domain (SSD)-containing proteins – NPC1 and Patched1.
Speaker Biography: Dr Xin Gong is a postdoctoral research associate at the Department of Molecular Biology, Princeton University. His overarching research focus is to explore the principle of cholesterol metabolism, which is important for cardiovascular health, using structural biology, biochemical and biophysical approaches. He has resolved several structures of critical components in cholesterol metabolism pathways, including the SREBP pathway (which is the pivotal hub that transcriptionally regulates the synthesis and uptake of cholesterol and other lipids), the intracellular cholesterol trafficking pathway and the reverse cholesterol transport pathway. He solved the crystal structures of the essential domains of two central players in the yeast SREBP pathway, Sre1 and Scp1, and the EM structure of their complex. These structures and extensive biochemical characterizations provided an important framework for the mechanistic understanding of the SREBP pathway. Moreover, Dr. Gong has solved the cryo-EM structures of human NPC1 and ABCA1, two essential membrane transport proteins involved in cholesterol trafficking/transport, both of which are important in human physiology. Recently, Dr. Gong has solved the cryo-EM structure of another sterol-sensing domain (SSD)-containing protein – human Patched1, which provides critical insight into the functional mechanism of SSD-containing proteins.