Cheol-Young Maeng

Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism

The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the human hepatitis B virus surface proteins with a broadly neutralizing activity in vivo. We present the crystal structures of HzKR127 Fab and its complex with a major epitope peptide. In the complex structure, the bound peptide forms a type IV β-turn followed by 310 helical turn, the looped-out conformation of which provides a structural basis for broad neutralization. Upon peptide binding, the antibody undergoes a dramatic complementarity determining region H3 lid opening. To understand the structural implication of the virus neutralization, we carried out comprehensive alanine-scanning mutagenesis of all complementarity determining region residues in HzKR127 Fab. The functional mapping of the antigen-combining site demonstrates the specific roles of major binding determinants in antigen binding, contributing to the rational design for maximal humanization and affinity maturation of the antibody.

Cecropin A-melittin hybrid peptide exerts its antifungal effects by damaging on the plasma membranes of Trichosporon beigelii

To elucidate the effect of the peptide derived from cecropin A(1-8)-melittin(1-12) having potent antifungal activity without cytotoxicity against eukaryotic cell on the fungal cell membranes, Trichosporon beigelii protoplasts were prepared. The protoplasts treated with the peptide not only failed to regenerate the fungal cell walls but also disrupted the membrane, indicating that the peptide exerts its antifungal activity by acting on the plasma membranes.