biostudies-literatureUnknown301(7)Espinosa-Vinals CAcylated domains (ADs), like that of the Bordetella pertussis adenylate cyclase toxin (CyaA), are structures found in all pore-forming toxins from the family of Repeat-in-ToXin (RTX) proteins. These AD segments are fatty-acylated on ε-amino groups of conserved lysine residues, such as the K860 and K983 residues of CyaA. The ε-amide-linked acyl chains are essential for toxin activity and promote irreversible membrane insertion of the CyaA molecule, thus enabling the toxin to translocate its N-terminal adenyl cyclase enzyme domain into the host cell cytoplasm. In parallel, the membrane-inserted CyaA molecules can oligomerize into cation-selective pores in the plasma membrane. Here, we show that the attached acyl chains are not only crucial for membrane insertion of the toxin but also play anThe Journal of biological chemistry110392https://www.ebi.ac.uk/biostudies/studies/S-EPMC12332401biostudies-literatureAcyl chains stabilize the acylated domain and determine the receptor-mediated interaction of the Bordetella adenylate cyclase toxin with cell membrane.PMC12332401Sebo PEspinosa-Vinals CBumba LOsickova AJurnecka DStransky JOsicka RfalseAcyl chains stabilize the acylated domain and determine the receptor-mediated interaction of the Bordetella adenylate cyclase toxin with cell membrane.Acylated domains (ADs), like that of the Bordetella pertussis adenylate cyclase toxin (CyaA), are structures found in all pore-forming toxins from the family of Repeat-in-ToXin (RTX) proteins. These AD segments are fatty-acylated on ε-amino groups of conserved lysine residues, such as the K860 and K983 residues of CyaA. The ε-amide-linked acyl chains are essential for toxin activity and promote irreversible membrane insertion of the CyaA molecule, thus enabling the toxin to translocate its N-terminal adenyl cyclase enzyme domain into the host cell cytoplasm. In parallel, the membrane-inserted CyaA molecules can oligomerize into cation-selective pores in the plasma membrane. Here, we show that the attached acyl chains are not only crucial for membrane insertion of the toxin but also play an2025-01-01T00:00:00Z2025 Jul2026-04-15T19:07:11.132Z2026-04-07T14:00:43.765ZS-EPMC123324014054358510.1016/j.jbc.2025.110392