Current dogma assumes that lipid asymmetry in biological membranes is actively maintained and dispensable for cell viability. The inner (cytoplasmic) membrane (IM) of 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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698083 | PMC |
http://dx.doi.org/10.1126/sciadv.ads0244 | DOI Listing |
Sci Adv
January 2025
Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Microbiol Spectr
December 2024
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Subcell Biochem
December 2024
Department of Macromolecular Structure, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.
Viral particles consist essentially of a proteinaceous capsid that protects the genome and is also involved in many functions during the virus life cycle. In structurally simple viruses, the capsid consists of a number of copies of the same, or a few different proteins organized into a symmetric oligomer. Structurally complex viruses present a larger variety of components in their capsids than simple viruses.
View Article and Find Full Text PDFFEBS Lett
December 2024
Department of Medical Chemistry, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Japan.
Phospholipids are asymmetrically distributed in the plasma membrane (PM), and scramblases disrupt this asymmetry by shuffling phospholipids. We recently identified mouse Tmem63b as a membrane structure-responsive scramblase. Tmem63b belongs to the TMEM63/OSCA family of ion channels; however, the conservation of the scramblase activity within this family remains unclear.
View Article and Find Full Text PDFmBio
December 2024
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Unlabelled: Bacteria have evolved diverse strategies to ensure survival under nutrient-limited conditions, where rapid energy generation is not achievable. Here, we performed a transposon insertion site sequencing loss-of-function screen to identify genes that promote pathogen fitness in stationary phase. We discovered that the aintenance of ipid symmetry (Mla) pathway, which is crucial for transferring phospholipids from the outer to the inner membrane, is critical for stationary phase fitness.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!