A Conserved Archaeal Pathway for Tail-Anchored Membrane Protein Insertion

Eukaryotic tail-anchored ( TA) membrane proteins are inserted into the endoplasmic reticulum by a posttranslational TRC40 pathway, but no comparable pathway is known in other domains of life. The crystal structure of an archaebacterial TRC40 sequence homolog bound to ADP.AlF4- reveals characteristic features of eukaryotic TRC40, including a zinc-mediated dimer and a large hydrophobic groove. Moreover, archaeal TRC40 interacts with the transmembrane domain of TA substrates and directs their membrane insertion. Thus, the TRC40 pathway is more broadly conserved than previously recognized.