Faculty, Staff and Student Publications
Publication Date
1-3-2025
Journal
Science Advances
Abstract
Current dogma assumes that lipid asymmetry in biological membranes is actively maintained and dispensable for cell viability. The inner (cytoplasmic) membrane (IM) of Escherichia coli is asymmetric. However, the molecular mechanism that maintains this uneven distribution is unknown. We engineered a conditionally lethal phosphatidylethanolamine (PE)-deficient mutant in which the presence of cardiolipin (CL) on the periplasmic leaflet of the IM is essential for viability, revealing a mechanism that provides CL on the desired leaflet of the IM. CL synthase (ClsA) flips its catalytic cytoplasmic domain upon depletion of PE to supply nonbilayer-prone CL in the periplasmic leaflet of the IM for cell viability. In the presence of a physiological amount of PE, osmotic down-shock induces a topological inversion of ClsA, establishing the biological relevance of membrane protein reorientations in wild-type cells. These findings support a flippase-less mechanism for maintaining membrane lipid asymmetry in biogenic membranes by self-organization of a lipid-synthesizing enzyme.
Keywords
Transferases (Other Substituted Phosphate Groups), Cardiolipins, Escherichia coli, Membrane Proteins, Cell Membrane, Phosphatidylethanolamines, Escherichia coli Proteins, Mutation
DOI
10.1126/sciadv.ads0244
PMID
39752486
PMCID
PMC11698083
PubMedCentral® Posted Date
1-3-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes