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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 Ca2+ response, suggesting that while CD95 aggregation controls the implementation of the apoptotic signal, both aggregation and conformation are required to implement the Ca2+ pathway. © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

Citation

Eden Lebrault, Christelle Oblet, Keerthi Kurma, Nicolas Levoin, Robin Jeannet, Mickael Jean, Pierre Vacher, Patrick Legembre. CD95L concatemers highlight different stoichiometries of CD95-mediated apoptotic and nonapoptotic pathways. European journal of immunology. 2024 Jan;54(1):e2350626

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PMID: 37837385

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