Abstract
Ten years ago, high-throughput genetic interaction analyses revealed an abundant and widely conserved protein complex residing in the endoplasmic reticulum (ER) membrane. Dubbed the ER membrane protein complex (EMC), its disruption has since been found to affect wide-ranging processes, including protein trafficking, organelle communication, ER stress, viral maturation, lipid homeostasis, and others. However, its molecular function has remained enigmatic. Recent studies suggest a role for EMC during membrane protein biogenesis. Biochemical reconstitution experiments show that EMC can directly mediate the insertion of transmembrane domains (TMDs) into the lipid bilayer. Given the large proportion of genes encoding membrane proteins, a central role for EMC as a TMD insertion factor can explain its high abundance, wide conservation, and pleiotropic phenotypes.
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