propeptide; cysteine protease; unfolding; Der p 1; stability; mechanism of activation; allergen; zymogen; fluorescence quenching
Abstract :
[en] BACKGROUND: Papain-like proteases (CA1) are synthesized as inactive precursors carrying an N-terminal propeptide, which is further removed under acidic conditions to generate active enzymes. METHODS: To have a better insight into the mechanism of activation of this protease family, we compared the pH unfolding of the zymogen and the mature form of the mite cysteine protease Der p 1. RESULTS: We showed that the presence of the propeptide does not significantly influence the pH-induced unfolding of the catalytic domain but does affect its fluorescence properties by modifying the exposure of the tryptophan 192 to the solvent. In addition, we demonstrated that the propeptide displays weaker pH stability than the protease domain confirming that the unfolding of the propeptide is the key event in the activation process of the zymogen. GENERAL SIGNIFICANCE: Finally, we show, using thermal denaturation and enzymatic activity measurements, that whatever the pH value, the propeptide does not stabilize the structure of the catalytic domain but very interestingly, prevents its autolysis.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Chevigne, A.
Dumez, Marie-Eve ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Dumoulin, Mireille ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Matagne, André ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Jacquet, A.
Galleni, Moreno ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Language :
English
Title :
Comparative study of mature and zymogen mite cysteine protease stability and pH unfolding.
Publication date :
2010
Journal title :
Biochimica et Biophysica Acta
ISSN :
0006-3002
eISSN :
1878-2434
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
1800
Issue :
9
Pages :
937-945
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2010 Elsevier B.V. All rights reserved.
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Levicar N., Strojnik T., Kos J., Dewey R.A., Pilkington G.J., Lah T.T. Lysosomal enzymes, cathepsins in brain tumour invasion. J. Neurooncol. 2002, 58:21-32.
Kikuchi Y., Takai T., Kuhara T., Ota M., Kato T., Hatanaka H., Ichikawa S., Tokura T., Akiba H., Mitsuishi K., Ikeda S., Okumura K., Ogawa H. Crucial commitment of proteolytic activity of a purified recombinant major house dust mite allergen Der p1 to sensitization toward IgE and IgG responses. J. Immunol. 2006, 177:1609-1617.
Yasuda Y., Kaleta J., Bromme D. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv. Drug Deliv. Rev. 2005, 57:973-993.
Fujishima A., Imai Y., Nomura T., Fujisawa Y., Yamamoto Y., Sugawara T. The crystal structure of human cathepsin L complexed with E-64. FEBS Lett. 1997, 407:47-50.
Drenth J., Jansonius J.N., Koekoek R., Swen H.M., Wolthers B.G. Structure of papain. Nature 1968, 218:929-932.
Meno K., Thorsted P.B., Ipsen H., Kristensen O., Larsen J.N., Spangfort M.D., Gajhede M., Lund K. The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen. J. Immunol. 2005, 175:3835-3845.
Wiederanders B. Structure-function relationships in class CA1 cysteine peptidase propeptides. Acta Biochim. Pol. 2003, 50:691-713.
Karrer K.M., Peiffer S.L., DiTomas M.E. Two distinct gene subfamilies within the family of cysteine protease genes. Proc. Natl. Acad. Sci. U.S.A. 1993, 90:3063-3067.
Groves M.R., Taylor M.A., Scott M., Cummings N.J., Pickersgill R.W., Jenkins J.A. The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft. Structure 1996, 4:1193-1203.
Kreusch S., Fehn M., Maubach G., Nissler K., Rommerskirch W., Schilling K., Weber E., Wenz I., Wiederanders B. An evolutionarily conserved tripartite tryptophan motif stabilizes the prodomains of cathepsin L-like cysteine proteases. Eur. J. Biochem. 2000, 267:2965-2972.
Groves M.R., Coulombe R., Jenkins J., Cygler M. Structural basis for specificity of papain-like cysteine protease proregions toward their cognate enzymes. Proteins 1998, 32:504-514.
Vernet T., Berti P.J., de Montigny C., Musil R., Tessier D.C., Menard R., Magny M.C., Storer A.C., Thomas D.Y. Processing of the papain precursor. The ionization state of a conserved amino acid motif within the Pro region participates in the regulation of intramolecular processing. J. Biol. Chem. 1995, 270:10838-10846.
Reddy V.Y., Zhang Q.Y., Weiss S.J. Pericellular mobilization of the tissue-destructive cysteine proteinases, cathepsins B, L, and S, by human monocyte-derived macrophages. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:3849-3853.
Schilling K., Pietschmann S., Fehn M., Wenz I., Wiederanders B. Folding incompetence of cathepsin L-like cysteine proteases may be compensated by the highly conserved, domain-building N-terminal extension of the proregion. Biol. Chem. 2001, 382:859-865.
Pietschmann S., Fehn M., Kaulmann G., Wenz I., Wiederanders B., Schilling K. Foldase function of the cathepsin S proregion is strictly based upon its domain structure. Biol. Chem. 2002, 383:1453-1458.
Huete-Perez J.A., Engel J.C., Brinen L.S., Mottram J.C., McKerrow J.H. Protease trafficking in two primitive eukaryotes is mediated by a prodomain protein motif. J. Biol. Chem. 1999, 274:16249-16256.
Menard R., Carmona E., Takebe S., Dufour E., Plouffe C., Mason P., Mort J.S. Autocatalytic processing of recombinant human procathepsin L. Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitro. J. Biol. Chem. 1998, 273:4478-4484.
Vernet T., Khouri H.E., Laflamme P., Tessier D.C., Musil R., Gour-Salin B.J., Storer A.C., Thomas D.Y. Processing of the papain precursor. Purification of the zymogen and characterization of its mechanism of processing. J. Biol. Chem. 1991, 266:21451-21457.
Bromme D., Bonneau P.R., Lachance P., Wiederanders B., Kirschke H., Peters C., Thomas D.Y., Storer A.C., Vernet T. Functional expression of human cathepsin S in Saccharomyces cerevisiae. Purification and characterization of the recombinant enzyme. J. Biol. Chem. 1993, 268:4832-4838.
Pungercar J.R., Caglic D., Sajid M., Dolinar M., Vasiljeva O., Pozgan U., Turk D., Bogyo M., Turk V., Turk B. Autocatalytic processing of procathepsin B is triggered by proenzyme activity. FEBS J. 2009, 276:660-668.
Linnevers C.J., McGrath M.E., Armstrong R., Mistry F.R., Barnes M.G., Klaus J.L., Palmer J.T., Katz B.A., Bromme D. Expression of human cathepsin K in Pichia pastoris and preliminary crystallographic studies of an inhibitor complex. Protein Sci. 1997, 6:919-921.
Ishidoh K., Takeda-Ezaki M., Watanabe S., Sato N., Aihara M., Imagawa K., Kikuchi M., Kominami E. Analysis of where and which types of proteinases participate in lysosomal proteinase processing using bafilomycin A1 and Helicobacter pylori Vac A toxin. J. Biochem. 1999, 125:770-779.
Kihara M., Kakegawa H., Matano Y., Murata E., Tsuge H., Kido H., Katunuma N. Chondroitin sulfate proteoglycan is a potent enhancer in the processing of procathepsin L. Biol. Chem. 2002, 383:1925-1929.
Lecaille F., Bromme D., Lalmanach G. Biochemical properties and regulation of cathepsin K activity. Biochimie 2008, 90:208-226.
Vasiljeva O., Dolinar M., Pungercar J.R., Turk V., Turk B. Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans. FEBS Lett. 2005, 579:1285-1290.
Caglic D., Pungercar J.R., Pejler G., Turk V., Turk B. Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide-mature enzyme interactions. J. Biol. Chem. 2007, 282:33076-33085.
Jerala R., Zerovnik E., Kidric J., Turk V. pH-induced conformational transitions of the propeptide of human cathepsin L. A role for a molten globule state in zymogen activation. J. Biol. Chem. 1998, 273:11498-11504.
Chevigne A., Barumandzadeh R., Groslambert S., Cloes B., Dehareng D., Filee P., Marx J.C., Frere J.M., Matagne A., Jacquet A., Galleni M. Relationship between propeptide pH unfolding and inhibitory ability during ProDer p 1 activation mechanism. J. Mol. Biol. 2007, 374:170-185.
Majerle A., Jerala R. Protein inhibitors form complexes with procathepsin L and augment cleavage of the propeptide. Arch. Biochem. Biophys. 2003, 417:53-58.
Kaulmann G., Palm G.J., Schilling K., Hilgenfeld R., Wiederanders B. The crystal structure of a Cys25→Ala mutant of human procathepsin S elucidates enzyme-prosequence interactions. Protein Sci. 2006, 15:2619-2629.
Turk B., Turk V., Turk D. Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol. Chem. 1997, 378:141-150.
Edwin F., Jagannadham M.V. Sequential unfolding of papain in molten globule state. Biochem. Biophys. Res. Commun. 1998, 252:654-660.
Huet J., Looze Y., Bartik K., Raussens V., Wintjens R., Boussard P. Structural characterization of the papaya cysteine proteinases at low pH. Biochem. Biophys. Res. Commun. 2006, 341:620-626.
Haq S.K., Rasheedi S., Khan R.H. Characterization of a partially folded intermediate of stem bromelain at low pH. Eur. J. Biochem. 2002, 269:47-52.
Fairhead M., Kelly S.M., van der Walle C.F. A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation. Biochem. Biophys. Res. Commun. 2008, 366:862-867.
Dumez M.E., Teller N., Mercier F., Tanaka T., Vandenberghe I., Vandenbranden M., Devreese B., Luxen A., Frere J.M., Matagne A., Jacquet A., Galleni M., Chevigne A. Activation mechanism of recombinant Der p 3 allergen zymogen: contribution of cysteine protease Der p 1 and effect of propeptide glycosylation. J. Biol. Chem. 2008, 283:30606-30617.
Chua K.Y., Stewart G.A., Thomas W.R., Simpson R.J., Dilworth R.J., Plozza T.M., Turner K.J. Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases. J. Exp. Med. 1988, 167:175-182.
Zhang J., Hamilton J.M., Garrod D.R., Robinson C. Interactions between mature Der p 1 and its free prodomain indicate membership of a new family of C1 peptidases. Allergy 2007, 62:1302-1309.
Takai T., Mineki R., Nakazawa T., Takaoka M., Yasueda H., Murayama K., Okumura K., Ogawa H. Maturation of the activities of recombinant mite allergens Der p 1 and Der f 1, and its implication in the blockade of proteolytic activity. FEBS Lett. 2002, 531:265-272.
Lakowicz J. Principles of Fluorescence Spectroscopy 1983, Plenum Press New York.
Takai T., Mizuuchi E., Kikuchi Y., Nagamune T., Okumura K., Ogawa H. Glycosylation of recombinant proforms of major house dust mite allergens Der p 1 and Der f 1 decelerates the speed of maturation. Int. Arch. Allergy Immunol. 2006, 139:181-187.
Maubach G., Schilling K., Rommerskirch W., Wenz I., Schultz J.E., Weber E., Wiederanders B. The inhibition of cathepsin S by its propeptide-specificity and mechanism of action. Eur. J. Biochem. 1997, 250:745-750.
Van Gilst M., Hudson B.S. Histidine-tryptophan interactions in T4 lysozyme: 'anomalous' pH dependence of fluorescence. Biophys. Chem. 1996, 63:17-25.
Thomas B., Heap P., Carswell F. Ultrastructural localization of the allergen Der p I in the gut of the house dust mite Dermatophagoides pteronyssinus. Int. Arch. Allergy Appl. Immunol. 1991, 94:365-367.
Takai T., Kato T., Sakata Y., Yasueda H., Izuhara K., Okumura K., Ogawa H. Recombinant Der p 1 and Der f 1 exhibit cysteine protease activity but no serine protease activity. Biochem. Biophys. Res. Commun. 2005, 328:944-952.
Takai T., Kato T., Yasueda H., Okumura K., Ogawa H. Analysis of the structure and allergenicity of recombinant pro- and mature Der p 1 and Der f 1: major conformational IgE epitopes blocked by prodomains. J. Allergy Clin. Immunol. 2005, 115:555-563.
Takai T., Kato T., Hatanaka H., Inui K., Nakazawa T., Ichikawa S., Mitsuishi K., Ogawa H., Okumura K. Modulation of allergenicity of major house dust mite allergens Der f 1 and Der p 1 by interaction with an endogenous ligand. J. Immunol. 2009, 183:7958-7965.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
