S. J. Arbes, . Jr, P. J. Gergen, L. Elliott, and D. C. Zeldin, Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey, J. Allergy Clin. Immunol, vol.116, pp.377-383, 2005.

G. D'amato, L. Cecchi, S. Bonini, C. Nunes, I. Annesi-maesano et al., Allergenic pollen and pollen allergy in Europe, Allergy, vol.62, pp.976-990, 2007.

G. J. Burbach, L. M. Heinzerling, C. Röhnelt, K. C. Bergmann, H. Behrendt et al., )LEN study (2009) Ragweed sensitization in Europe-GA(2)LEN study suggests increasing prevalence, Allergy, vol.64, issue.2, pp.664-665

M. L. Oswalt and G. D. Marshall, Ragweed as an example of worldwide allergen expansion, Allergy Asthma Clin. Immunol, vol.4, pp.130-135, 2008.

M. Smith, L. Cecchi, C. A. Skjøth, G. Karrer, and B. ?ikoparija, Common ragweed: a threat to environmental health in Europe, Environ. Int, vol.61, pp.115-126, 2013.

B. Floch, V. Groeme, R. Chabre, H. Baron-bodo, V. Nony et al., New insights into ragweed pollen allergens, vol.15, p.63, 2015.

R. Asero, N. Wopfner, P. Gruber, G. Gadermaier, and F. Ferreira, Artemisia and Ambrosia hypersensitivity: co-sensitization or co-recognition?, Clin. Exp. Allergy, vol.36, pp.658-665, 2006.

G. Gadermaier, N. Wopfner, M. Wallner, M. Egger, A. Didierlaurent et al., Arraybased profiling of ragweed and mugwort pollen allergens, Allergy, vol.63, pp.1543-1549, 2008.

J. Bouley, R. Groeme, M. Le-mignon, K. Jain, H. Chabre et al., Identification of the cysteine protease Amb a 11 as a novel major allergen from short ragweed, J. Allergy Clin. Immunol, vol.136, pp.1055-1064, 2015.

L. Bussières, . Bordas-le, V. Floch, I. Bulder, H. Chabre et al., Recombinant fusion proteins assembling Der p 1 and Der p 2 allergens from Dermatophagoides pteronyssinus, Int. Arch. Allergy Immunol, vol.153, pp.141-151, 2010.

D. Choudhury, S. Roy, C. Chakrabarti, S. Biswas, and J. K. Dattagupta, Production and recovery of recombinant propapain with high yield, Phytochemistry, vol.70, pp.465-472, 2009.

J. G. Lees, B. R. Smith, F. Wien, A. J. Miles, and B. A. Wallace, CDtool-an integrated software package for circular dichroism spectroscopic data processing, analysis, and archiving, Anal. Biochem, vol.332, pp.285-289, 2004.

I. H. Van-stokkum, H. J. Spoelder, M. Bloemendal, R. Van-grondelle, and F. C. Groen, Estimation of protein secondary structure and error analysis from circular dichroism spectra, Anal. Biochem, vol.191, pp.110-118, 1990.

L. Whitmore and B. A. Wallace, DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data, Nucleic Acids Res, vol.32, pp.668-673, 2004.

W. Kabsch, Acta Crystallogr. D Biol. Crystallogr, vol.66, pp.125-132, 2010.

L. C. Storoni, A. J. Mccoy, and R. J. Read, Likelihood-enhanced fast rotation functions, Acta Crystallogr. D Biol. Crystallogr, vol.60, pp.432-438, 2004.

M. E. Than, M. Helm, D. J. Simpson, F. Lottspeich, R. Huber et al., The 2.0 Å crystal structure and substrate specificity of the KDEL-tailed cysteine endopeptidase functioning in programmed cell death of Ricinus communis endosperm, J. Mol. Biol, vol.336, pp.1103-1116, 2004.

S. Roy, D. Choudhury, P. Aich, J. K. Dattagupta, and S. Biswas, The structure of a thermostable mutant of pro-papain reveals its activation mechanism, Acta Crystallogr. D Biol. Crystallogr, vol.68, pp.1591-1603, 2012.

G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller et al., Global Phasing Ltd, 2011.

P. Emsley and K. Cowtan, Coot: model-building tools for molecular graphics, Acta Crystallogr. D Biol. Crystallogr, vol.60, pp.2126-2132, 2004.

A. Razafindratsita, N. Saint-lu, L. Mascarell, N. Berjont, T. Bardon et al., Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation, J. Allergy Clin. Immunol, vol.120, pp.278-285, 2007.

M. Novinec and B. Lenar?i?, Papain-like peptidases: structure, function, and evolution, BioMol Concepts, vol.4, pp.287-308, 2013.

K. Meno, P. B. Thorsted, H. Ipsen, O. Kristensen, J. N. Larsen et al., The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen, J. Immunol, vol.175, pp.3835-3845, 2005.

S. De-halleux, E. Stura, L. Vanderelst, V. Carlier, M. Jacquemin et al., Three-dimensional structure and IgE-binding properties of mature fully active Der p 1, a clinically relevant major allergen, J. Allergy Clin. Immunol, vol.117, pp.571-576, 2006.

I. G. Kamphuis, K. H. Kalk, M. B. Swarte, and J. Drenth, Structure of papain refined at 1.65 Å resolution, J. Mol. Biol, vol.179, pp.233-256, 1984.

B. Floch, V. Le-mignon, M. Bouley, J. Groeme, R. Jain et al., Identification of novel short ragweed pollen allergens using combined transcriptomic and immunoproteomic approaches, PLoS One, vol.10, p.136258, 2015.

G. Gadermaier, M. Hauser, and F. Ferreira, Allergens of weed pollen: an overview on recombinant and natural molecules, Methods, vol.66, pp.55-66, 2014.

D. Burtin, H. Chabre, B. Olagnier, A. Didierlaurent, M. N. Couret et al., Production of native and modified recombinant Der p 1 molecules in tobacco plants, Clin. Exp. Allergy, vol.39, pp.760-770, 2009.

D. Brömme, F. S. Nallaseth, and B. Turk, Production and activation of recombinant papain-like cysteine proteases, Methods, vol.32, pp.199-206, 2004.

V. Turk, V. Stoka, O. Vasiljeva, M. Renko, T. Sun et al., Cysteine cathepsins: from structure, function and regulation to new frontiers, Biochim. Biophys. Acta, vol.1824, pp.68-88, 2012.

H. Gunawan, T. Takai, S. Ikeda, K. Okumura, and H. Ogawa, Protease activity of allergenic pollen of cedar, cypress, juniper, birch and ragweed, Allergol. Int, vol.57, pp.83-91, 2008.

H. Gunawan, T. Takai, S. Kamijo, X. L. Wang, S. Ikeda et al., Characterization of proteases, proteins, and eicosanoid-like substances in soluble extracts from allergenic pollen grains, Int. Arch. Allergy Immunol, vol.147, pp.276-288, 2008.

B. Wiederanders, Structure-function relationships in class CA1 cysteine peptidase propeptides, Acta Biochim. Pol, vol.50, pp.691-713, 2003.

G. Kaulmann, G. J. Palm, K. Schilling, R. Hilgenfeld, and B. Wiederanders, The crystal structure of a Cys25 3 Ala mutant of human procathepsin S elucidates enzyme-prosequence interactions, Protein Sci, vol.15, pp.2619-2629, 2006.

C. M. Stack, C. R. Caffrey, S. M. Donnelly, A. Seshaadri, J. Lowther et al., Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica, J. Biol. Chem, vol.283, pp.9896-9908, 2008.

J. Sivaraman, M. Lalumière, R. Ménard, and M. Cygler, Crystal structure of wild-type human procathepsin K, Protein Sci, vol.8, pp.283-290, 1999.

M. R. Groves, M. A. Taylor, M. Scott, N. J. Cummings, R. W. Pickersgill et al., The prosequence of procaricain forms an ?-helical domain that prevents access to the substrate-binding cleft, Structure, vol.4, pp.1193-1203, 1996.

A. Chevigné, R. Barumandzadeh, S. Groslambert, B. Cloes, D. Dehareng et al., Relationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 activation mechanism, J. Mol. Biol, vol.374, pp.170-185, 2007.

I. V. Demidyuk, A. V. Shubin, E. V. Gasanov, and S. V. Kostrov, Propeptides as modulators of functional activity of proteases, 2010.

, Biomol. Concepts, vol.1, pp.305-322

J. Eder and A. R. Fersht, Pro-sequence-assisted protein folding, Mol. Microbiol, vol.16, pp.609-614, 1995.

B. Wiederanders, G. Kaulmann, and K. Schilling, Functions of propeptide parts in cysteine proteases, Curr. Protein Pept. Sci, vol.4, pp.309-326, 2003.

V. Nandana, S. Singh, A. N. Singh, and V. K. Dubey, Procerain B, a cysteine protease from Calotropis procera, requires N-terminus proregion for activity: cDNA cloning and expression with pro-sequence. Protein Expr, Purif, vol.103, pp.16-22, 2014.

W. Paul, J. Amiss, R. Try, U. Praekelt, R. Scott et al., Correct processing of the kiwifruit protease actinidin in transgenic tobacco requires the presence of the C-terminal propeptide, Plant Physiol, vol.108, pp.261-268, 1995.

S. Dutta, D. Choudhury, J. K. Dattagupta, and S. Biswas, C-terminal extension of a plant cysteine protease modulates proteolytic activity through a partial inhibitory mechanism, FEBS J, vol.278, pp.3012-3024, 2011.

M. Schmid, D. Simpson, F. Kalousek, and C. Gietl, A cysteine endopeptidase with a C-terminal KDEL motif isolated from castor bean endosperm is a marker enzyme for the ricinosome, a putative lytic compartment, Planta, vol.206, pp.466-475, 1998.

T. Okamoto, T. Minamikawa, G. Edward, V. Vakharia, E. Herman et al., Posttranslational removal of the carboxyl-terminal KDEL of the cysteine protease SH-EP occurs prior to maturation of the enzyme, J. Biol. Chem, vol.274, pp.11390-11398, 1999.

R. Deb, F. Shakib, K. Reid, C. , and H. , Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D, J. Biol. Chem, vol.282, pp.36808-36819, 2007.

O. A. Henriquez, K. Den-beste, E. K. Hoddeson, C. A. Parkos, A. Nusrat et al., House dust mite allergen Der p 1 effects on sinonasal epithelial tight junctions, Int. Forum Allergy Rhinol, vol.3, pp.630-635, 2013.

L. Reubsaet, J. Meerding, R. Giezeman, I. De-kleer, B. Arets et al., Der p 1-induced CD4? FOXP3? GATA3? T cells have suppressive properties and contribute to the polarization of the TH2-associated response, J. Allergy Clin. Immunol, vol.132, pp.1440-1444, 2013.

M. H. Yi, H. P. Kim, K. Y. Jeong, C. R. Kim, T. Y. Kim et al., House dust mite allergen Der f 1 induces IL-8 in human basophilic cells via ROS-ERK and p38 signal pathways, Cytokine, vol.75, pp.356-364, 2015.

E. E. Comoy, J. Pestel, C. Duez, G. A. Stewart, C. Vendeville et al., The house dust mite allergen, Dermatophagoides pteronyssinus, promotes type 2 responses by modulating the balance between IL-4 and IFN-?, J. Immunol, vol.160, pp.2456-2462, 1998.

L. Gough, H. F. Sewell, and F. Shakib, The proteolytic activity of the major dust mite allergen Der p 1 enhances the IgE antibody response to a bystander antigen, Clin. Exp. Allergy, vol.31, pp.1594-1598, 2001.

M. D. Chapman, S. Wünschmann, and A. Pomés, Proteases as Th2 adjuvants, Curr. Allergy Asthma Rep, vol.7, pp.363-367, 2007.

P. T. Cunningham, C. E. Elliot, J. C. Lenzo, A. G. Jarnicki, A. N. Larcombe et al., Sensitizing and Th2 adjuvant activity of cysteine protease allergens, Int. Arch. Allergy Immunol, vol.158, pp.347-358, 2012.

P. A. Karplus and K. Diederichs, Linking crystallographic model and data quality, Science, vol.336, pp.1030-1033, 2012.

P. Moingeon,

V. Baron-bodo, V. Bordas-le, L. Floch, P. B. Mascarell, L. Berjont et al.,

R. Groeme, S. Airouche, D. Kopecný, J. Jaekel, and M. Savko, Nathalie Short Ragweed Pollen Structural and Functional Characterization of the Major Allergen Amb a 11 from, vol.291, pp.13076-13087, 2016.

, J. Biol. Chem

, Access the most updated version of this article at doi