Mechanical reinforcement of protein L fromFinegoldia magnapoints to a new bind-and-search mechanism

Abstract

AbstractSeveral significant bacterial pathogens in humans secrete surface proteins that bind antibodies in order to protect themselves from the adaptive immune response and have evolved to operate under the mechanical sheer generated by mucus flow, coughing or urination. Protein L is secreted byFinegoldia magnaand has several antibody-binding domains. These domains have two antibody-binding sites with vastly different avidity and the function of the second weaker binding interface is currently unknown. Here we use magnetic tweezers and covalent attachment via HaloTag and SpyTag to expose Protein L to unfolding forces in the absence and presence of antibody-ligands. We find that antibody binding increases the mechanical stability of protein L. Using the change in mechanical stability as a binding reporter, we determined that the low-avidity binding site is acting as a mechano-sensor. We propose a novel mechanism where the high-avidity binding site engages the tether, while the low-avidity binding site acts as a mechano-sensor, allowing bacteria to sample the antibody surface concentration and localize its search during successful binding under strain.SignificanceIt is well known that bacteria have an arsenal of tools to invade and to avoid dislocation. Based on the molecular response of a protein used by anaerobic bacteria to attach to antibodies and disrupt the immune system, here we report on a force-sensor-like behavior, triggered by antibody clusters and force. This pseudo-catch bond between bacteria and antibodies is activated through a second binding site which has lower avidity to antibodies, and which acts as a mechanical sensor, potentially regulating the search radii of the bacterium. Understanding of the bacteria attachment mechanism is of great importance toward developing new antibiotics and mechano-active drugs.