Background: The ability of mycoplasma to cause chronic infections suggests that they evolved mechanisms to bypass or counter their host’s immune system. We previously characterized the MIB-MIP complex, a widespread system in mycoplasma that selectively captures and cleaves IgG. Methods: In this work, we further studied this system by solving the 3D structure of MIB-MIP bound to their target antibody. Based on these structural data, we analyzed the functionality of the system in vitro and in cellulo.Results: Solving the 3D structure highlights the molecular determinants of the MIB-MIP mechanism. In particular, it suggests that MIB-MIP can target and cleave antibodies that are already bound to an antigen, which was then successfully verified in vitro. We also show that the MIB-MIP system can bind and degrade the three main classes of antibodies (IgG, sIgA and IgM), but that in cellulo this function is focused solely on antibodies targeting the cell surface and ignores non-specific immunoglobulins. We also provide a comparative analysis of the 4 pairs of MIB-MIP encoded in the genome of the model Mycoplasma mycoides subsp. capri GM12. Our results show that they are functionally redundant and fully cross-reactive, suggesting that their sequence diversity is linked to antigenic variation.Conclusion: We showed that mycoplasma have a mechanism dedicated to destroying specific antibodies, the main components of the humoral response. The in vivo function of this system is to be further studied, but our data shed new light on the host-pathogen interaction of these bacteria.< Réduire