A pH-sensitive motif in an outer membrane protein activates bacterial membrane vesicle production.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 Aug 2024
13 Aug 2024
Historique:
received:
16
11
2023
accepted:
02
08
2024
medline:
14
8
2024
pubmed:
14
8
2024
entrez:
13
8
2024
Statut:
epublish
Résumé
Outer membrane vesicles (OMVs) produced by Gram-negative bacteria have key roles in cell envelope homeostasis, secretion, interbacterial communication, and pathogenesis. The facultative intracellular pathogen Salmonella Typhimurium increases OMV production inside the acidic vacuoles of host cells by changing expression of its outer membrane proteins and modifying the composition of lipid A. However, the molecular mechanisms that translate pH changes into OMV production are not completely understood. Here, we show that the outer membrane protein PagC promotes OMV production through pH-dependent interactions between its extracellular loops and surrounding lipopolysaccharide (LPS). Structural comparisons and mutational studies indicate that a pH-responsive amino acid motif in PagC extracellular loops, containing PagC-specific histidine residues, is crucial for OMV formation. Molecular dynamics simulations suggest that protonation of histidine residues leads to changes in the structure and flexibility of PagC extracellular loops and their interactions with the surrounding LPS, altering membrane curvature. Consistent with that hypothesis, mimicking acidic pH by mutating those histidine residues to lysine increases OMV production. Thus, our findings reveal a mechanism for sensing and responding to environmental pH and for control of membrane dynamics by outer membrane proteins.
Identifiants
pubmed: 39138228
doi: 10.1038/s41467-024-51364-z
pii: 10.1038/s41467-024-51364-z
doi:
Substances chimiques
Bacterial Outer Membrane Proteins
0
Lipopolysaccharides
0
Histidine
4QD397987E
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6958Subventions
Organisme : Howard Hughes Medical Institute (HHMI)
ID : CC30430
Informations de copyright
© 2024. The Author(s).
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