1.O.8. The Entropy-driven Translocation of Disordered Proteins through the Gram-positive Bacterial Cell Wall (EdT) Family
In Gram-positive bacteria, a thick cross-linked cell wall separates the membrane from the extracellular space. Some surface-exposed proteins, such as the Listeria monocytogenes actin nucleation-promoting factor, ActA, remain associated with the bacterial membrane but somehow thread through tens of nanometres of cell wall to expose their amino termini to the exterior. Halladin et al. 2021 reported that entropy enables the translocation of disordered transmembrane proteins through the Gram-positive cell wall. They described a physical model, which predicts that the entropic constraint imposed by a thin periplasm is sufficient to drive the translocation of an intrinsically disordered protein such as ActA across a porous barrier similar to a peptidoglycan cell wall. They experimentally validated their model and showed that ActA translocation depends on the cell-envelope dimensions and the disordered-protein length, and that translocation is reversible. Disordered regions of eukaryotic proteins can translocate Gram-positive cell walls via entropy. They proposed that entropic forces are sufficient to drive the translocation of specific proteins to the outer surface (Halladin et al. 2021).