Daniel Rosenbaum, Associate Professor, Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, will give a talk titled, "Molecular mechanism of cholesterol homeostasis in mammalian cells."

ABSTRACT

The cholesterol-sensing protein Scap induces cholesterol synthesis by transporting membrane-bound sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi apparatus for proteolytic activation. We have used cryo-EM to elucidate structures of Scap alone and in complex with the ER retention protein Insig. These structures revealed different conformations of Scap, with different arrangements of its transmembrane helices and luminal domain. We postulate that this conformational change halts Scap transport of SREBPs and inhibits cholesterol synthesis, and we are currently working to understand the molecular mechanism of cholesterol binding and allosteric control of the Scap-Insig-SREBP complex.