Unravelling Antibody-Induced Mechanical Stability of Antigen: Insights from Single-Molecule Studies

Abstract

AbstractThe intricate nature of antigen-antibody interactions plays a pivotal role in immunological responses. Despite the multitude of ligand-binding sites on antigens, the influence of antibodies on their mechanical stability remains elusive. This study elucidates the impact of IgM, the largest antibody isotype, on the mechanical stability of protein L, a bacterial superantigen, using single-molecule magnetic tweezers and steered molecular dynamics. Our findings reveal a concentration-dependent elevation in mechanical stability induced by IgM, as demonstrated by prolonged unfolding dwell times. Through steered molecular dynamics simulations, we elucidate the distinct mechanical responses of protein L binding interfaces at various IgM complex states, highlighting their synergistic effect on IgM dimer complex stability. Notably, this enhanced response stems from the altered unfolding pathway of protein L upon IgM interaction, providing significant insights into the generic mechanisms governing antibody-induced mechanical stability of antigenic substrates in physiological conditions, shedding light on the underlying folding dynamics and molecular mechanics of antigen-antibody interaction.