Pleiner, T.*; Pinton Tomaleri, G.*; Januszyk, K.*; Inglis, A.J.; Hazu, M.; Voorhees, R.M. (2020) Structural basis for membrane insertion by the human ER membrane protein complex. Science 369(6502):433-436.
The ER membrane protein complex (EMC) is an essential transmembrane domain insertase involved in the co- and post-translational insertion of a wide range of membrane proteins. Due to the absence of structural data, it was unclear how the EMC functions as an insertase. We used a nanobody-based purification strategy that Tino developed during his PhD (Pleiner et al., 2015, eLife) to purify the human EMC, which was critical to determining its first ever structure by cryo-EM in collaboration with other lab members. Armed with structural information, we used cell-based fluorescent reporter assays to gain mechanistic insights into EMC function. We found that the EMC uses local membrane thinning and polar intramembrane residues to reduce the energetic barrier for insertion into the lipid bilayer.