CD95L concatemers highlight different stoichiometries of CD95‐mediated apoptotic and nonapoptotic pathways Article Swipe

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Jurkat cells Random hexamer Apoptosis Concatemer Biology Cell biology Fas receptor Dimer Stoichiometry Programmed cell death Biophysics Molecular biology Biochemistry Chemistry T cell Immunology Immune system Gene Genome Organic chemistry

Eden Lebrault , Christelle Oblet , Keerthi Kurma , Nicolas Levoin , Robin Jeannet , Mickaël Jean , Pierre Vacher , Patrick Legembre ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1002/eji.202350626 · OA: W4387640135

To better understand the stoichiometry of CD95L required to trigger apoptotic and nonapoptotic signals, we generated several CD95L concatemers from dimer to hexamer conjugated via a flexible link (GGGGS) 2 . These ligands reveal that although the hexameric structure is the best stoichiometry to trigger cell death, a dimer is sufficient to induce the apoptotic response in CD95‐sensitive Jurkat cells. Interestingly, only trimeric and hexameric forms can implement a potent Ca 2+ response, suggesting that while CD95 aggregation controls the implementation of the apoptotic signal, both aggregation and conformation are required to implement the Ca 2+ pathway.