8.A.142. The PAT Intramembrane Chaperone Complex (PAT) Family
In eukaryotes, the majority of membrane proteins are inserted, modified and folded in the endoplasmic reticulum (ER). Very little is known about how multi-spanning membrane proteins with several TMSs are assembled within the membrane. During the assembly of TMSs, interactions between polar or charged amino acids typically stabilize the final folded configuration. TMSs with hydrophilic amino acyl residues are chaperoned during the co-translational biogenesis. Chitwood and Hegde 2020 identified the PAT complex, an abundant obligate heterodimer of the widely conserved ER-resident membrane proteins CCDC47 and Asterix. The PAT complex engages nascent TMSs that contain unshielded hydrophilic side chains within the lipid bilayer, and it disengages concomitant with substrate folding. Cells that lack either subunit of the PAT complex show reduced biogenesis of numerous multi-spanning membrane proteins. Thus, the PAT complex is an intramembrane chaperone that protects TMSs during assembly to minimize misfolding of multi-spanning membrane proteins and maintain cellular protein homeostasis.