. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?,

. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?, , pp.1354-1373, 1019.

. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?,

. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?,

. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?,

. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?,

P. ?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-?-references-1.-siman and A. Brik, Chemical and semisynthesis of posttranslationally modified proteins, Org. Biomol. Chem, vol.10, pp.5684-5697, 2012.

H. Ry?lavá, V. Doubnerová, D. Kavan, and O. Van?k, Effect of posttranslational modifications on enzyme function and assembly, J. Proteomics, vol.92, pp.80-109, 2013.

I. Linhartová, L. Bumba, J. Ma?ín, M. Basler, R. Osi?ka et al., RTX proteins: a highly diverse family secreted by a common mechanism, FEMS Microbiol. Rev, vol.34, pp.1076-1112, 2010.

A. Chenal, A. C. Sotomayor-perez, and D. Ladant, Structure and function of RTX toxins, The Comprehensive Sourcebook of Bacterial Protein Toxins, 2015.

J. P. Issartel, V. Koronakis, and C. Hughes, Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation, Nature, vol.351, pp.759-761, 1991.

R. A. Welch, Pore-forming cytolysins of gram-negative bacteria, Mol. Microbiol, vol.5, pp.521-528, 1991.

M. Hackett, L. Guo, J. Shabanowitz, D. F. Hunt, and E. L. Hewlett, Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis, Science, vol.266, pp.433-435, 1994.

T. Basar, V. Havlícek, S. Bezousková, M. Hackett, and P. Sebo, Acylation of lysine 983 is sufficient for toxin activity of Bordetella pertussis adenylate cyclase. Substitutions of alanine 140 modulate acylation site selectivity of the toxin acyltransferase CyaC, J. Biol. Chem, vol.276, pp.348-354, 2001.

N. P. Greene, A. Crow, C. Hughes, and V. Koronakis, Structure of a bacterial toxin-activating acyltransferase, Proc. Natl. Acad. Sci. USA, vol.112, pp.3058-3066, 2015.

G. Fedele, I. Schiavoni, I. Adkins, N. Klimova, and P. Sebo, Invasion of dendritic cells, macrophages and neutrophils by the bordetella adenylate cyclase toxin: a subversive move to fool host immunity, Toxins (Basel), vol.9, p.293, 2017.

R. Benz, Channel formation by RTX-toxins of pathogenic bacteria: basis of their biological activity, Biochim. Biophys. Acta, vol.1858, pp.526-537, 2016.

D. Ladant and A. Ullmann, Bordatella pertussis adenylate cyclase: a toxin with multiple talents, Trends Microbiol, vol.7, pp.172-176, 1999.

J. Vojtova, J. Kamanova, and P. Sebo, Bordetella adenylate cyclase toxin: a swift saboteur of host defense, Curr. Opin. Microbiol, vol.9, pp.69-75, 2006.

N. Guiso, Bordetella adenylate cyclase-hemolysin toxins, Toxins, vol.9, p.277, 2017.

J. C. Karst, A. C. Sotomayor-pérez, J. I. Guijarro, B. Raynal, A. Chenal et al., Calmodulin-induced conformational and hydrodynamic changes in the catalytic domain of Bordetella pertussis adenylate cyclase toxin, Biochemistry, vol.49, pp.318-328, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00512114

D. P. O'brien, D. Durand, A. Voegele, V. Hourdel, M. Davi et al., Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis, PLoS Biol, vol.15, p.2004486, 2017.

N. H. Carbonetti, Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools, Future Microbiol, vol.5, pp.455-469, 2010.

A. Chenal and D. Ladant, Bioengineering of Bordetella pertussis adenylate cyclase toxin for antigen-delivery and immunotherapy, Toxins (Basel), vol.10, p.302, 2018.

P. Glaser, H. Sakamoto, J. Bellalou, A. Ullmann, and A. Danchin, Secretion of cyclolysin, the calmodulin-sensitive adenylate cyclase-haemolysin bifunctional protein of Bordetella pertussis, 1988.

, EMBO J, vol.7, pp.3997-4004

J. Bellalou, H. Sakamoto, D. Ladant, C. Geoffroy, and A. Ullmann, Deletions affecting hemolytic and toxin activities of Bordetella pertussis adenylate cyclase, Infect. Immun, vol.58, pp.3242-3247, 1990.

J. Bellalou, D. Ladant, and H. Sakamoto, Synthesis and secretion of Bordetella pertussis adenylate cyclase as a 200-kilodalton protein, Infect. Immun, vol.58, pp.1195-1200, 1990.

H. Sakamoto, J. Bellalou, P. Sebo, and D. Ladant, Bordetella pertussis adenylate cyclase toxin. Structural and functional independence of the catalytic and hemolytic activities, J. Biol. Chem, vol.267, pp.13598-13602, 1992.

C. Martín, M. A. Requero, J. Masin, I. Konopasek, F. M. Goñi et al., Membrane restructuring by Bordetella pertussis adenylate cyclase toxin, a member of the RTX toxin family, J. Bacteriol, vol.186, pp.3760-3765, 2004.

J. C. Karst, R. Barker, U. Devi, M. J. Swann, M. Davi et al., Identification of a region that assists membrane insertion and translocation of the catalytic domain of Bordetella pertussis CyaA toxin, J. Biol. Chem, vol.287, pp.9200-9212, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-01423063

J. Masin, A. Osickova, A. Sukova, R. Fiser, P. Halada et al., Negatively charged residues of the segment linking the enzyme and cytolysin moieties restrict the membrane-permeabilizing capacity of adenylate cyclase toxin, Sci. Rep, vol.6, p.29137, 2016.

O. Subrini, A. C. Sotomayor-pérez, A. Hessel, J. Spiaczka-karst, E. Selwa et al., Characterization of a membrane-active peptide from the Bordetella pertussis CyaA toxin, J. Biol. Chem, vol.288, pp.32585-32598, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00937043

A. Voegele, O. Subrini, N. Sapay, D. Ladant, and A. Chenal, Membrane-active properties of an amphitropic peptide from the CyaA toxin translocation region, Toxins (Basel), vol.9, p.369, 2017.

E. M. Barry, A. A. Weiss, I. E. Ehrmann, M. C. Gray, E. L. Hewlett et al., Bordetella pertussis adenylate cyclase toxin and hemolytic activities require a second gene, cyaC, for activation, J. Bacteriol, vol.173, pp.720-726, 1991.

J. Masin, M. Basler, O. Knapp, M. El-azami-el-idrissi, E. Maier et al., Acylation of lysine 860 allows tight binding and cytotoxicity of Bordetella adenylate cyclase on CD11b-expressing cells, Biochemistry, vol.44, pp.12759-12766, 2005.

V. Bouchez, T. Douché, M. Dazas, S. Delaplane, M. Matondo et al., Characterization of post-translational modifications and cytotoxic properties of the adenylate-cyclase hemolysin produced by various bordetella pertussis and bordetella parapertussis isolates, Toxins (Basel), vol.9, p.304, 2017.

C. Bauche, A. Chenal, O. Knapp, C. Bodenreider, R. Benz et al., Structural and functional characterization of an essential RTX subdomain of Bordetella pertussis adenylate cyclase toxin, J. Biol. Chem, vol.281, pp.16914-16926, 2006.

A. Chenal, J. I. Guijarro, B. Raynal, M. Delepierre, and D. Ladant, RTX calcium binding motifs are intrinsically disordered in the absence of calcium: implication for protein secretion, J. Biol. Chem, vol.284, pp.1781-1789, 2009.
URL : https://hal.archives-ouvertes.fr/pasteur-00364637

A. C. Sotomayor-pérez, J. C. Karst, M. Davi, J. I. Guijarro, D. Ladant et al., Characterization of the regions involved in the calcium-induced folding of the intrinsically disordered RTX motifs from the bordetella pertussis adenylate cyclase toxin, J. Mol. Biol, vol.397, pp.534-549, 2010.

A. Chenal, J. C. Karst, A. C. Sotomayor-pérez, A. K. Wozniak, B. Baron et al., Calcium-induced folding and stabilization of the intrinsically disordered RTX domain of the CyaA toxin, Biophys. J, vol.99, pp.3744-3753, 2010.
URL : https://hal.archives-ouvertes.fr/pasteur-01509576

A. C. Sotomayor-pérez, D. Ladant, and A. Chenal, Calcium-induced folding of intrinsically disordered repeat-in-toxin (RTX) motifs via changes of protein charges and oligomerization states, J. Biol. Chem, vol.286, pp.16997-17004, 2011.

A. C. Sotomayor-pérez, J. C. Karst, D. Ladant, and A. Chenal, Mean net charge of intrinsically disordered proteins: experimental determination of protein valence by electrophoretic mobility measurements, Methods Mol. Biol, vol.896, pp.331-349, 2012.

A. C. Sotomayor-pérez, O. Subrini, A. Hessel, D. Ladant, and A. Chenal, Molecular crowding stabilizes both the intrinsically disordered calcium-free state and the folded calcium-bound state of a repeat in toxin (RTX) protein, J. Am. Chem. Soc, vol.135, pp.11929-11934, 2013.

A. C. Sotomayor-pérez, D. Ladant, and A. Chenal, Disorder-to-order transition in the CyaA toxin RTX domain: implications for toxin secretion, Toxins (Basel), vol.7, pp.1-20, 2014.

D. P. O'brien, B. Hernandez, D. Durand, V. Hourdel, A. C. Sotomayor-pérez et al., Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion, Sci. Rep, vol.5, p.14223, 2015.

L. Bumba, J. Masin, P. Macek, T. Wald, L. Motlova et al., Calcium-driven folding of RTX domain b-rolls ratchets translocation of RTX proteins through type I secretion ducts, Mol. Cell, vol.62, pp.47-62, 2016.

S. E. Cannella, V. Y. Ntsogo-enguéné, M. Davi, C. Malosse, A. C. Sotomayor-pérez et al., ) Stability, structural and functional properties of a monomeric, calcium-loaded adenylate cyclase toxin, CyaA, from Bordetella pertussis, Sci. Rep, vol.7, p.42065, 2017.

D. P. O'brien, A. C. Perez, J. Karst, S. E. Cannella, V. Y. Enguéné et al., Calcium-dependent disorder-to-order transitions are central to the secretion and folding of the CyaA toxin of Bordetella pertussis, the causative agent of whooping cough, Toxicon, vol.149, pp.37-44, 2018.

T. Rose, P. Sebo, J. Bellalou, and D. Ladant, Interaction of calcium with Bordetella pertussis adenylate cyclase toxin. Characterization of multiple calcium-binding sites and calcium-induced conformational changes, J. Biol. Chem, vol.270, pp.26370-26376, 1995.

R. A. Welch, RTX toxin structure and function: a story of numerous anomalies and few analogies in toxin biology, Curr. Top. Microbiol. Immunol, vol.257, pp.85-111, 2001.

R. Veneziano, C. Rossi, A. Chenal, J. M. Devoisselle, D. Ladant et al., Bordetella pertussis adenylate cyclase toxin translocation across a tethered lipid bilayer, Proc. Natl. Acad. Sci. USA, vol.110, pp.20473-20478, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01093165

J. Novak, O. Cerny, A. Osickova, I. Linhartova, J. Masin et al., Structure-function relationships underlying the capacity of bordetella adenylate cyclase toxin to disarm host phagocytes, Toxins (Basel), vol.9, p.300, 2017.

J. C. Karst, V. Y. Ntsogo-enguéné, S. E. Cannella, O. Subrini, A. Hessel et al., Calcium, acylation, and molecular confinement favor folding of Bordetella pertussis adenylate cyclase CyaA toxin into a monomeric and cytotoxic form, J. Biol. Chem, vol.289, pp.30702-30716, 2014.
URL : https://hal.archives-ouvertes.fr/pasteur-01408931

J. Cox and M. Mann, MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification, Nat. Biotechnol, vol.26, pp.1367-1372, 2008.

J. Cox, N. Neuhauser, A. Michalski, R. A. Scheltema, J. V. Olsen et al., Andromeda: a peptide search engine integrated into the MaxQuant environment, J. Proteome Res, vol.10, pp.1794-1805, 2011.

V. Hourdel, S. Volant, D. P. O'brien, A. Chenal, J. Chamot-rooke et al., MEMHDX: an interactive tool to expedite the statistical validation and visualization of large HDX-MS datasets, Bioinformatics, vol.32, pp.3413-3419, 2016.
URL : https://hal.archives-ouvertes.fr/pasteur-01377055

J. C. Karst, A. C. Sotomayor-pérez, D. Ladant, and A. Chenal, Estimation of intrinsically disordered protein shape and timeaveraged apparent hydration in native conditions by a combination of hydrodynamic methods, Methods Mol. Biol, vol.896, pp.163-177, 2012.
URL : https://hal.archives-ouvertes.fr/pasteur-01423306

G. Karimova, C. Fayolle, S. Gmira, A. Ullmann, C. Leclerc et al., Charge-dependent translocation of Bordetella pertussis adenylate cyclase toxin into eukaryotic cells: implication for the in vivo delivery of CD8(+) T cell epitopes into antigen-presenting cells, Proc. Natl. Acad. Sci. USA, vol.95, pp.12532-12537, 1998.

S. Gmira, G. Karimova, and D. Ladant, Characterization of recombinant Bordetella pertussis adenylate cyclase toxins carrying passenger proteins, Res. Microbiol, vol.152, pp.889-900, 2001.

D. Ladant, Interaction of Bordetella pertussis adenylate cyclase with calmodulin. Identification of two separated calmodulinbinding domains, J. Biol. Chem, vol.263, pp.2612-2618, 1988.

P. Sebo, P. Glaser, H. Sakamoto, and A. Ullmann, High-level synthesis of active adenylate cyclase toxin of Bordetella pertussis in a reconstructed Escherichia coli system, Gene, vol.104, pp.19-24, 1991.

G. D. Westrop, E. K. Hormozi, N. A. Da-costa, R. Parton, and J. G. Coote, Bordetella pertussis adenylate cyclase toxin: proCyaA and CyaC proteins synthesised separately in Escherichia coli produce active toxin in vitro, Gene, vol.180, pp.91-99, 1996.

M. El-azami-el-idrissi, C. Bauche, J. Loucka, R. Osicka, P. Sebo et al., Interaction of Bordetella pertussis adenylate cyclase with CD11b/CD18: role of toxin acylation and identification of the main integrin interaction domain, J. Biol. Chem, vol.278, pp.38514-38521, 2003.

G. V. Semisotnov, N. A. Rodionova, O. I. Razgulyaev, V. N. Uversky, &. Gripas et al., Study of the "molten globule" intermediate state in protein folding by a hydrophobic fluorescent probe, Biopolymers, vol.31, pp.119-128, 1991.

D. P. O'brien, S. Brier, D. Ladant, D. Durand, A. Chenal et al., SEC-SAXS and HDX-MS: a powerful combination. The case of the calcium-binding domain of a bacterial toxin, Biotechnol. Appl. Biochem, vol.65, pp.62-68, 2018.