Type III secretion system effector proteins are mechanically labile
Marc-André LeBlanc, Morgan R. Fink, Thomas T. Perkins, Marcelo C. Sousa
Abstract
Significance The type III secretion system (T3SS) is an important virulence factor that enables some bacteria to directly inject effector proteins into host cells, facilitating colonization. To be secreted, effector proteins must be unfolded, and tightly packed proteins like GFP cannot be secreted through the T3SS, leading to the model that effector proteins have low thermodynamic stability. We show that two model effector proteins have thermodynamic stabilities similar to tightly packed proteins (GFP and ubiquitin) but are much more mechanically labile. These results strongly suggest that mechanical stability predicts whether a protein is compatible with secretion through the T3SS and may shed light on the distinct evolutionary pressures that resulted in the sequence divergence of effector proteins from their nonsecreted homologues.