Membrane protein homeostasis
A well-orchestrated interplay of protein biosynthesis and degradation is required to maintain protein homeostasis. Our lab is particularly interested in the regulation of membrane protein biosynthesis and assembly. The human genome encodes thousands of membrane proteins that are the predominant target of all modern drugs. Yet, little is known about how they are inserted, folded, and assembled at the endoplasmic reticulum (ER). Biogenesis factors called insertases facilitate membrane protein insertion into the lipid bilayer. The highly conserved ER membrane protein complex (EMC) has recently emerged as a major insertase of many endogenous, as well as viral membrane proteins.
As part of a team in the Voorhees lab @ Caltech, Tino helped solved the first structure of the human EMC and gained mechanistic insights into its function and assembly in human cells. We could also define a selectivity filter in the EMC that regulates substrate selection to favor insertion of so-called tail-anchored membrane proteins destined for the ER, while discriminating against those destined for the mitchondrial outer membrane.
Pleiner, T.*, Tomaleri, G.P.*, Januszyk, K.* et al. (2020) Structural basis for membrane insertion by the human ER membrane protein complex. Science, 369, 433-436.
Pleiner, T. et al. (2021) WNK1 is an assembly factor for the human ER membrane protein complex. Mol Cell, 81, 2693-2704.e12.
Pleiner, T.*, Hazu, M.*, Tomaleri, G.P.* et al. (2023) A selectivity filter in the EMC limits protein mislocalization to the ER. J. Cell Biol. 222(8):e202212007.