Protein L, secreted as a superantigen by Finegoldia magna, has several domains, including membrane-spanning (A), and evolutionarily conserved (B). Credit: Soham Chakraborty
IgM, or Immunoglobulin M — the largest antibody in the human body and essential for early defence against infections — goes beyond simply binding pathogens. It mechanically fortifies bacterial toxins, making it easier for the immune system to neutralise them1.
Shubhasis Haldar, and colleagues at the S.N. Bose National Centre for Basic Sciences, Kolkata, investigated the interaction between IgM antibodies and Protein L, a superantigen found on the surface of Finegoldia magna, a bacterium that causes toxic shock syndrome. This protein disrupts normal immune function by sticking to antibodies in unusual ways.
Using single-molecule magnetic tweezers, the researchers gently tugged at the IgM–Protein L binding sites to observe their response to mechanical stress. Attaching to IgM made the Protein L more stable, locking its shape in place and preventing it from unfolding or binding abnormally. The higher the concentration of IgM in the system, the greater the resistance to stress.
Computer simulations revealed that Protein L can latch on to the antibodies at two different sites. Whether IgM associates with one or both sites dictates the shift in the protein’s structure, and the order in which it unravels under mechanical stress.
The finding shifts the common perception of antibodies from being mere chemical keys to structural engineers that alter molecular properties and could pave the way for new strategies to counter dangerous superantigens.
