Open AccessEntropy-driven translocation of disordered proteins through the Gram-positive bacterial cell wall
Author(s) -
David K. Halladin,
Fabian E. Ortega,
Katharine M. Ng,
Matthew J. Footer,
Nenad S. Mitić,
Saša N. Malkov,
Ajay Gopinathan,
Kerwyn Casey Huang,
Julie A. Theriot
Publication year - 2021
Publication title -
nature microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.305
H-Index - 79
ISSN - 2058-5276
DOI - 10.1038/s41564-021-00942-8
Subject(s) - gram , chromosomal translocation , cell wall , microbiology and biotechnology , bacterial translocation , bacterial cell structure , bacterial protein , chemistry , entropy (arrow of time) , escherichia coli proteins , biology , bacteria , biophysics , physics , genetics , gene , biochemistry , thermodynamics
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 terminus to the exterior. Here, we report that entropy enables the translocation of disordered transmembrane proteins through the Gram-positive cell wall. We build 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. We experimentally validate our model and show that ActA translocation depends on the cell-envelope dimensions and disordered-protein length, and that translocation is reversible. We also show that disordered regions of eukaryotic proteins can translocate Gram-positive cell walls via entropy. We propose that entropic forces are sufficient to drive the translocation of specific proteins to the outer surface.