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The cryo-EM structure reveals a completely new mechanism, which resembles the juji gatamé armlock technique used in ju-jitsu or judo (Figure 34). MIB and MIP encircle the Fab fragment, holding it firmly in their arm domains. The linker between the antibody s CH and VH domains is twisted and put in a favourable orientation to be cleaved by MIP. In addition, the conformation of the Fab in the MIB-MIP-Fab complex is drastically impaired. The VL and the VH fragments are twisted out of alignment and the antigen-binding site is torn apart. The distance between the VL and the VH complementary-determining regions (CDRs) is nearly twice the usual distance measured in an isolated Fab. These data reveal that the MIB-MIP complex, and MIB alone, are able to promote the dissociation of the antigen-antibody complex.

These high-resolution data show that MIB and MIP use an unprecedented mechanism to dissociate the antigen- antibody complex and capture and inactivate the antibody by proteolytic cleavage. They highlight the key role of MIB and MIP in the host immunity evasion by mycoplasmas, and indicate that MIB and MIP would be therapeutic targets of interest in veterinary and human health.

In addition to their relevance to the field of host-pathogen interaction, MIB and MIP could also become important biotechnology tools. The ability of MIB to promote the dissociation of the antibody-antigen complexes is unique. This property opens exciting perspectives to develop new biotechnological tools in the immunoglobulin field to manipulate antibodies or to dissociate antibodies bound to their antigen.

Fig. 34: Artistic representation of MIB and MIP in action at the surface of a mycoplasma cell. Atomic models of full length MIB and MIP are represented as surfaces in blue and red respectively. Immunoglobulins are represented as surfaces with their light chain in yellow and their heavy chains in orange. First, an immunoglobulin bound to a mycoplasma surface antigen is recognised by MIB and displaced from this antigen. The VH domain of the immunoglobulin is shifted away from its initial position freeing the linker between the CH and VH domains of the Fab. Subsequently, the protease MIP is recruited, the VH domain is cleaved off, and finally the cleaved antibody released from the cell surface.

PRINCIPAL PUBLICATION AND AUTHORS

The mycoplasma surface proteins MIB and MIP promote the dissociation of the antibody-antigen interaction, P. Nottelet (a), L. Bataille (b), G. Gourgues (b), R. Anger (a), C. Lartigue (b), P. Sirand-Pugnet (b), E. Marza (a), R. Fronzes (a), Y. Arfi (b), Sci. Adv. 7, 10 (2021); https:/doi.org/10.1126/sciadv.abf2403 (a) Structure and Function of Bacterial Nanomachines, UMR 5234, Univ. Bordeaux, CNRS, Institut Européen de Chimie et Biologie, Pessac (France) (b) Univ. Bordeaux, INRAE, Biologie du Fruit et Pathologie, UMR 1332, Villenave d Ornon (France)

REFERENCES

[1] Y. Arfi et al., PNAS 113, 5406-5411 (2016).