Protein translocation is mediated by oligomers of the SecY complex with one SecY copy forming the channel.

Many proteins are translocated across the bacterial plasma membrane by the interplay of the cytoplasmic ATPase SecA with a protein-conducting channel, formed from the evolutionarily conserved heterotrimeric SecY complex. Here, we have used purified E. coli components to address the mechanism of translocation. Disulfide bridge crosslinking demonstrates that SecA transfers both the signal sequence and the mature region of a secreted substrate into a single SecY molecule. However, protein translocation involves oligomers of the SecY complex, because a SecY molecule defective in translocation can be rescued by linking it covalently with a wild-type SecY copy. SecA interacts through one of its domains with a nontranslocating SecY copy and moves the polypeptide chain through a neighboring SecY copy. Oligomeric channels with only one active pore likely mediate protein translocation in all organisms.