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 ubiquitous protein-conducting channel SecY. Features conserved by its two duplicated halves suggest that their common ancestor was an antiparallel homodimeric channel. Structural searches with SecY’s halves detect exceptional similarity with the only other ubiquitous protein transporter, YidC. Their shared fold comprises a three-helix bundle interrupted by a helical hairpin. In YidC this hairpin is cytoplasmic and facilitates substrate delivery, whereas in SecY it is transmembrane and forms the substrate-binding lateral gate helices. In both, the three-helix bundle forms a protein-conducting hydrophilic groove, 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 transporters would reconstruct a key step in the evolution of cells.