How Cells Make Membrane Proteins

NIH Wednesday Afternoon Lecture
Our genomes encode ~5000 integral membrane proteins. These proteins are essential for sensing the environment, communication with other cells, transport of nutrients and metabolites, neurotransmission, and countless other physiologic processes. Newly made membrane proteins are first inserted into the endoplasmic reticulum membrane. The majority of these membrane proteins have to be weaved back and forth multiple times across the lipid bilayer, folded into a functional three-dimensional structure, and sometimes assembled with other subunits. Our research aims to understand how such complex membrane proteins are made correctly. We have taken a biochemical approach to identify and mechanistically dissect the factors involved in membrane protein targeting, insertion, folding, and assembly. We recently discovered an intramembrane chaperone that aids membrane protein folding. By studying how this chaperone functions, we revealed a new conceptual framework for membrane protein biogenesis. Ongoing efforts are aimed at understanding how multi-subunit complexes are assembled.
Manu Hegde, Ph.D., MRC Lab