Modification of the RTX domain cap by acyl chains of adapted length rules the formation of functional hemolysin pores.
Biochim Biophys Acta Biomembr
; 1866(5): 184311, 2024 Jun.
Article
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| MEDLINE
| ID: mdl-38570122
ABSTRACT
The acylated pore-forming Repeats in ToXin (RTX) cytolysins α-hemolysin (HlyA) and adenylate cyclase toxin (CyaA) preferentially bind to ß2 integrins of myeloid leukocytes but can also promiscuously bind and permeabilize cells lacking the ß2 integrins. We constructed a HlyA1-563/CyaA860-1706 chimera that was acylated either by the toxin-activating acyltransferase CyaC, using sixteen carbon-long (C16) acyls, or by the HlyC acyltransferase using fourteen carbon-long (C14) acyls. Cytolysin assays with the C16- or C14-acylated HlyA/CyaA chimeric toxin revealed that the RTX domain of CyaA can functionally replace the RTX domain of HlyA only if it is modified by C16-acyls on the Lys983 residue of CyaA. The C16-monoacylated HlyA/CyaA chimera was as pore-forming and cytolytic as native HlyA, whereas the C14-acylated chimera exhibited very low pore-forming activity. Hence, the capacity of the RTX domain of CyaA to support the insertion of the N-terminal pore-forming domain into the target cell membrane, and promote formation of toxin pores, strictly depends on the modification of the Lys983 residue by an acyl chain of adapted length.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Toxina de Adenilato Ciclasa
/
Proteínas Hemolisinas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Biomembr
/
Biochim. biophys. acta, Biomembr
/
Biochimica et biophysica acta. Biomembranes
Año:
2024
Tipo del documento:
Article
País de afiliación:
República Checa