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

Abstract

Cells 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.

Highlighting membrane protein structure and function: A celebration of the Protein Data Bank

“…In-depth analyses of the YidC and SecY structures and of the requirements for the biogenesis of different classes of integral MPs and secreted proteins shed light on the origins and evolution of the most ancient "translocators." Lewis and Hegde speculate that SecY originated as a YidC homolog formed of two hydrophilic grooves juxtaposed within an antiparallel homodimer (197). The proposed "molecular filiation" between the two major MP biogenesis factors offers a new perspective on a fundamental step in the evolution of macromolecular biological systems and cells.…”