A unified evolutionary origin for SecY and YidC
AbstractCells use transporters to move protein across membranes, but the most ancient transporters’ origins are unknown. Here, we analyse the protein-conducting channel SecY and deduce a plausible path to its evolution. We find that each of its pseudosymmetric halves consists of a three-helix bundle interrupted by a two-helix hairpin. Unexpectedly, we identify this same motif in the YidC family of membrane protein biogenesis factors, which is similarly ancient as SecY. In YidC, the two-helix hairpin faces the cytosol and facilitates substrate delivery, whereas in SecY it forms the substratebinding transmembrane helices of the lateral gate. We propose that SecY originated as a YidC homolog which formed a channel by juxtaposing two hydrophilic grooves in an antiparallel homodimer. Archaeal and eukaryotic YidC family members have repurposed this interface to heterodimerise with conserved partners. Unification of the two ancient membrane protein biogenesis factors reconstructs a key step in the evolution of cells.