Control of membrane barrier during bacterial type-III protein secretion

Svenja Hüsing (1) , Manuel Halte (1) , Ulf van Look (2) , Alina Guse (1) , Eric Gálvez (2) , Emmanuelle Charpentier (2) , David Blair (3) , Marc Erhardt (1) , T.T. Renault (4, 5)

1 HU Berlin - Humboldt-Universität zu Berlin = Humboldt University of Berlin = Université Humboldt de Berlin
2 MPUSP - Max Planck Unit for the Science of Pathogens [Berlin, Allemagne]
3 University of Utah
4 CNRS - Centre National de la Recherche Scientifique
5 UB - Université de Bordeaux

Abstract Type-III secretion systems (T3SSs) of the bacterial flagellum and the evolutionarily related injectisome are capable of translocating proteins with a remarkable speed of several thousand amino acids per second. Here, we investigate how T3SSs are able to transport proteins at such a high rate while preventing the leakage of small molecules. Our mutational and evolutionary analyses demonstrate that an ensemble of conserved methionine residues at the cytoplasmic side of the T3SS channel create a deformable gasket (M-gasket) around fast-moving substrates undergoing export. The unique physicochemical features of the M-gasket are crucial to preserve the membrane barrier, to accommodate local conformational changes during active secretion, and to maintain stability of the secretion pore in cooperation with a plug domain (R-plug) and a network of salt-bridges. The conservation of the M-gasket, R-plug, and salt-bridge network suggests a universal mechanism by which the membrane integrity is maintained during high-speed protein translocation in all T3SSs.

Domaines: Biochimie, Biologie Moléculaire; Bactériologie

Svenja Hüsing, Manuel Halte, Ulf van Look, Alina Guse, Eric Gálvez, et al.. Control of membrane barrier during bacterial type-III protein secretion. Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-24226-1⟩. ⟨hal-03442536⟩