Secreted bacterial proteins are targeted to and pushed through the translocon by the protein SecA. Because proteins must be threaded through the translocon in an unfolded state, the authors guessed that SecA might prevent folding of signal sequence–containing, and therefore secreted, proteins. Instead, they found just the reverse—SecA promotes the folding of proteins that lack export signals.
SecA bound to unfolded proteins even if they did not contain signal sequences. For proteins lacking an export signal, SecA promoted their folding to an active state. Once folded, SecA no longer binds, so secretion is thwarted. SecA did not have chaperone activity with signal sequence–containing proteins. What accounts for this difference is not yet known, but perhaps strong binding of SecA to the signal sequence disrupts its ability to promote folding. Yeast and human cells do not have a SecA homologue, but a different translocon-associated chaperone may perform an analogous function. ▪