S T R U C T U R A L B I O L O G Y

S C I E N T I F I C H I G H L I G H T S

4 6 H I G H L I G H T S 2 0 2 1 I

Taken together, these results reveal a unique molecular mechanism that might be an efficient metabolic switch at the crossroads of two metabolic superstructures (Figure 32). Understanding how these multifunctional

superstructures interact is essential for the development of new tailored therapeutic strategies, particularly for diseases entailing mitochondrial metabolism deficiencies like Alzheimer s disease.

PRINCIPAL PUBLICATION AND AUTHORS

Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination, G. Giachin (a), M. Jessop (b), R. Bouverot (a), S. Acajjaoui (a), M. Saidi (a), A. Chretien (a), M. Bacia-Verloop (b), L. Signor (b), P.J. Mas (b), A. Favier (b), E. Borel Meneroud (c), M. Hons (d), D.J. Hart (b), E. Kandiah (a), E. Boeri Erba (b), A. Buisson (c), G. Leonard (a), I. Gutsche (b), M. Soler-Lopez (a), Angew. Chem. Int. Ed. 60, 4689-4697 (2021); https:/doi.org/10.1002/anie.202011548 (a) ESRF (b) Institut de Biologie Structurale (IBS), Grenoble (France). (c) Grenoble Institut des Neurosciences (GIN), La Tronche (France). (d) EMBL, Grenoble (France).

REFERENCES

[1] G. Giachin et al., Front. Mol. Biosci. 3, 43 (2016). [2] M. Soler-Lopez et al., Genome Res. 21(3), 364 (2011). [3] M. Soler-Lopez et al., Bioessays 34, 532-541 (2012).

The Nano Juji-Gatame Armlock or how Mycoplasmas evade the host immune response by grappling and breaking down antibodies

The cryo-electron microscopy structure of mycoplasma MIB and MIP proteins in complex with a Fab, obtained at beamline CM01, reveals how these proteins capture and break down antibodies by performing a molecular judo armlock , shedding light on how mycoplasmas evade the host immune system.

Successful pathogens have developed multiple strategies to evade their host immune systems, in order to persist and propagate. Mycoplasmas are small bacteria able to colonise the mucosal surface of a wide range of hosts, including livestock species and humans. Many mycoplasma species are pathogenic and are naturally unresponsive to many antibiotics. The emergence of strains resistant to the few effective antibiotics (tetracycline in particular) is a cause for concern, in both the medical and veterinary fields. Most mycoplasmas are responsible for chronic respiratory, genital or urinary infections, suggesting that these bacteria are able to evade the host immune system. In particular, mycoplasmas need to escape antibody- mediated recognition and elude immune neutralisation

and clearance. Mycoplasmas have developed a two- protein system, referred to as the MIB-MIP system, based on Mycoplasma Immunoglobulin Binding (MIB) and Mycoplasma Immunoglobulin Protease (MIP), which respectively bind and cleave antibodies [1]. MIB recognises and captures the antibodies and subsequently recruits the serine protease MIP, which cuts off the antigen recognition domain VH, resulting in the inactivation of the antibodies.

The mechanism of action of the MIB-MIP system has been deciphered, using cryo-electron microscopy to visualise the molecular architecture of the system at the atomic scale. The crystal structures of the proteins MIB and MIP in complex with a goat IgG Fab (Figure 33) were solved using the ESRF Titan Krios electron microscope at beamline CM01, with an overall resolution of 2.8 Å.

Fig. 33: Structure of MIB and MIP proteins in complex with Fab. MIB and MIP are represented as surfaces in

blue and red respectively. The Fab is shown as ribbon representation with the light and heavy chains in green

and yellow respectively.