A conserved tryptophan in the acylated segment of RTX toxins controls their β₂ integrin-independent cell penetration.

ABSTRACT: The acylated Repeats in ToXins (RTX) leukotoxins, the adenylate cyclase toxin (CyaA) or α-hemolysin (HlyA), bind β₂ integrins of leukocytes but also penetrate cells lacking these receptors. We show that the indoles of conserved tryptophans in the acylated segments, W876 of CyaA and W579 of HlyA, are crucial for β₂ integrin-independent membrane penetration. Substitutions of W876 by aliphatic or aromatic residues did not affect acylation, folding, or the activities of CyaA W876L/F/Y variants on cells expressing high amounts of the β₂ integrin CR3. However, toxin activity of CyaA W876L/F/Y on cells lacking CR3 was strongly impaired. Similarly, a W579L substitution selectively reduced HlyA W579L cytotoxicity towards cells lacking β₂ integrins. Intrig

SUBMITTER: Osickova A 

PROVIDER: S-EPMC10392135 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature