<i>Mycobacterium tuberculosis</i> SatS is a chaperone for the SecA2 protein export pathway.

Miller, Brittany K; Hughes, Ryan; Ligon, Lauren S; Rigel, Nathan W; Malik, Seidu; Anjuwon-Foster, Brandon R; Sacchettini, James C; Braunstein, Miriam · Elife · 2019

basic_science · Level V

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Abstract

The SecA2 protein export system is critical for the virulence of <i>Mycobacterium tuberculosis</i>. However, the mechanism of this export pathway remains unclear. Through a screen for suppressors of a <i>secA2</i> mutant, we identified a new player in the mycobacterial SecA2 pathway that we named SatS for <u>S</u>ec<u>A</u>2 (<u>t</u>wo) <u>S</u>uppressor. In <i>M. tuberculosis</i>, 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 <i>M. tuberculosis</i> pathogenesis and in expanding our appreciation of the diversity among chaperones and protein export systems.

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