Tyrosine72 Residue at the Bottom of Rim Domain in LukF Crucial for the Sequential Binding of the Staphylococcal γ-Hemolysin to Human Erythrocytes

Abstract

Staphylococcal bi-component cytotoxins, leukocidin (Luk), Panton-Valentine leukocidin (PVL), and γ-hemolysin (Hlg) consist of LukF and LukS, LukF-PV and LukS-PV, and LukF and Hlg2, respectively, and Luk and Hlg share LukF. LukF-PV can not substitute for LukF for Hlg, despite 73% identity in amino acid sequence and close similarity in the 3-dimensional structure between them. Here, we demonstrated that the absence of hemolytic activity of LukF-PV in cooperation with Hlg2 is due to the failure of the binding of LukF-PV to human erythrocytes. We identified Y72 residue at the bottom of rim domain in LukF as the crucial residue for its binding, which is a prerequisite to the subsequent binding of Hlg2 to human erythrocytes. The data obtained showed that a mutant of LukF-PV in which T71 residue was replaced by the corresponding residue of LukF, Y72, endowed LukF-PV with the binding capability to human erythrocytes which was accompanied by its hemolytic activity in the presence of Hlg2.

• staphylococcal γ-hemolysin
• LukF
• LukF-PV
• binding sites to erythrocytes
• 3-dimensional structure