SatS is a chaperone for the SecA2 protein export pathway.

The SecA2 protein export system is critical for the virulence of . However, the mechanism of this export pathway remains unclear. Through a screen for suppressors of a mutant, we identified a new player in the mycobacterial SecA2 pathway that we named SatS for ec2 (wo) uppressor. In , SatS is required for the export of a subset of SecA2 substrates and for growth in macrophages. We further identify a role for SatS as a protein export chaperone. SatS exhibits multiple properties of a chaperone, including the ability to bind to and protect substrates from aggregation. Our structural studies of SatS reveal a distinct combination of a new fold and hydrophobic grooves resembling preprotein-binding sites of the SecB chaperone. These results are significant in better defining a molecular pathway for pathogenesis and in expanding our appreciation of the diversity among chaperones and protein export systems.