A unified evolutionary origin for the ubiquitous protein transporters SecY and YidC

Cells use transporters to move protein across membranes, but the origins of the most ancient transporters are unknown. Here, we analyse the protein-conducting channel SecY. Features conserved by its two duplicated halves suggest that their common ancestor was an antiparallel homodimeric channel. Structural searches with individual halves detect exceptional similarity with the YidC family of membrane protein transporters. Their shared fold comprises a three-helix bundle interrupted by a helical hairpin. In YidC this hairpin is cytosolic and facilitates substrate delivery, whereas in SecY it forms the substrate-binding transmembrane helices of the lateral gate. In both, the three-helix bundle forms a hydrophilic groove for translocation, delimited by a conserved hydrophobic residue. We propose that SecY originated as a homodimeric YidC homolog. Many YidC homologs now use this interface to heterodimerise with a conserved partner. Unification of the two ubiquitous protein transporter families reconstructs a key step in the evolution of cells.