RT Journal Article
T1 Activity modulation of the Escherichia coli F1FO ATP synthase by a designed antimicrobial peptide via cardiolipin sequestering
A1 Makowski, Marcin
A1 Almendro Vedia, Víctor Galileo
A1 Domingues, Marco M.
A1 Franco, Octavio L.
A1 López Montero, Iván
A1 Melo, Manuel
A1 Santos, Nuno C.
AB Most antimicrobial peptides (AMPs) exert their microbicidal activity through membrane permeabilization. The designed AMP EcDBS1R4 has a cryptic mechanism of action involving the membrane hyperpolarization of Escherichia coli, suggesting that EcDBS1R4 may hinder processes involved in membrane potential dissipation. We show that EcDBS1R4 can sequester cardiolipin, a phospholipid that interacts with several respiratory complexes of E. coli. Among these, F1FO ATP synthase uses membrane potential to fuel ATP synthesis. We found that EcDBS1R4 can modulate the activity of ATP synthase upon partition to membranes containing cardiolipin. Molecular dynamics simulations suggest that EcDBS1R4 alters the membrane environment of the transmembrane FO motor, impairing cardiolipin interactions with the cytoplasmic face of the peripheral stalk that binds the catalytic F1 domain to the FO domain. The proposed mechanism of action, targeting membrane protein function through lipid reorganization may open new venues of research on the mode of action and design of other AMPs.
PB Cell Press
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/115539
UL https://hdl.handle.net/20.500.14352/115539
LA eng
NO Activity modulation of the Escherichia coli F1FO ATP synthase by a designed antimicrobial peptide via cardiolipin sequestering Makowski, Marcin et al. iScience, Volume 26, Issue 7, 107004
NO Comunidad Autónoma de Madrid
NO Ministerio de Ciencia e Innovación
NO Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT-MCTES, Portugal)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 7 abr 2025