UCSF

Cells are surrounded and contained by a plasma membrane consisting of a double layerof fats and proteins. These proteins monitor and facilitate the movement of food, oxygen and messages in and out of the cell, and help neighboring cells communicate. Membrane proteins are manufactured in a cell compartment called the endoplasmic reticulum. Cellular machines called ribosomes manufacture proteins that need to be secreted or embedded into the cell’s membranes. As these proteins are made, they are pulled into the endoplasmic reticulum so they can be stabilized, folded correctly and inserted in the membrane. A cellular machine in this compartment’s membrane that aids this process is the endoplasmic reticulum membrane protein complex (EMC). The EMC is a large protein complex made up of ten subunits in mammalian cells. EMC’s intricate structure and large range of clients it stabilizes underscore its importance in maintaining protein homeostasis. Our studies illuminate the structural and mechanistic basis of EMC’s multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes. Beyond the molecular role of EMC, we build a genetic roadmap of the EMC in mammalian cells and helping decipher its crucial role in maintaining cholesterol homeostasis. Together, this work lays the framework for understanding both the molecular and physiological role of the EMC in mammalian cells.