Molecular basis of the anticancer, apoptotic and antibacterial activities of Bombyx mori Cecropin A

As Cecropin XJ, Cecropin A from Bombyx mori is one of the very few antimicrobial peptides having shown activity against esophageal cancer cells. It displays remarkable sequence-similarity to Cecropin XJ but slightly enhanced activity. In this work we show by NMR that both peptides are unstructured in solution but get structured in the presence of DPC micelles, mimicking the surface of biological membranes. In order to get insight into the molecular basis of its anticancer, antimicrobial and antifungal activity, we have investigated by MD simulations their interaction with a large variety of lipid bilayers mimicking cancer, mitochondrial, bacterial and fungal membranes. At variance with CecXJ, organized in two main helices, CecA tends to form a three helix bundle resulting in enhanced adaptability to its membrane targets. A specificity for the headgroup of phosphatidylserine and affinity for phosphatidylglycerol and cardiolipin may account for its selective targeting of cancer, bacterial and mitochondrial membranes, respectively.

Automated summary

Cecropin A and Cecropin XJ are antimicrobial peptides with activity against esophageal cancer cells. They exhibit different structural adaptations when interacting with DPC micelles, with CecA forming a three-helix bundle for enhanced adaptability. Specific interactions with different lipid bilayers may account for their selective targeting of cancer, bacterial, and mitochondrial membranes.