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Bombyx Mori Cecropin D Could Trigger Cancer Cell Apoptosis by Interacting with Mitochondrial Cardiolipin.

Abstract : Cecropin D is an antimicrobial peptide from Bombyx mori displaying anticancer and pro-apoptotic activities and, together with Cecropin XJ and Cecropin A, one of the very few peptides targeting esophageal cancer. Cecropin D displays poor similarity to other cecropins but a remarkable similarity in the structure and activity spectrum with Cecropin A and Cecropin XJ, offering the possibility to highlight key motifs at the base of the biological activity. In this work we show by NMR and MD simulations that Cecropin D is partially structured in solution and stabilizes its two-helix folding upon interaction with biomimetic membranes. Simulations show that Cecropin D strongly interacts with the surface of cancer cell biomimetic bilayers where it recognises the phosphatidylserine headgroup often exposed in the outer leaflet of cancerous cells by means of specific salt bridges. Cecropin D is also able to penetrate deeply in bilayers containing cardiolipin, a phospholipid found in mitochondria, causing significant destabilization in the lipid packing which might account for its pro-apoptotic activity. In bacterial membranes, phosphatidylglycerol and phosphatidylethanolamine act synergically by electrostatically attracting cecropin D and providing access to the membrane core, respectively.
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Soumis le : jeudi 21 juillet 2022 - 14:54:04
Dernière modification le : vendredi 5 août 2022 - 11:25:39




Francisco Ramos-Martin, Claudia Herrera-Léon, Nicola d'Amelio. Bombyx Mori Cecropin D Could Trigger Cancer Cell Apoptosis by Interacting with Mitochondrial Cardiolipin.. Biochimica et Biophysica Acta:Biomembranes, Elsevier, 2022, pp.184003. ⟨10.1016/j.bbamem.2022.184003⟩. ⟨hal-03735622⟩



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