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Activation processing of cathepsin H impairs recognition by its propeptide

  • Martin Horn , Lucie Dolečková-Marešová , Lubomír Rulíšek , Martin Máša , Olga Vasiljeva , Boris Turk , Tudeviin Gan-Erdene , Miroslav Baudyš and Michael Mareš
Published/Copyright: September 9, 2005

Abstract

Free propeptides are known to function as inhibitors of the parental mature cysteine cathepsins. This general rule, however, does not apply to the aminopeptidase cathepsin H. Screening of propeptide fragments for their inhibitory potency revealed no significant effect on the native mature cathepsin H. On the other hand, inhibitory interaction was established with recombinant cathepsin H that displays endopeptidase activity due to a lack of the mini-chain. This finding suggests that the propeptide-binding region is structurally rearranged during maturation processing and mini-chain formation, which impairs the effective recognition of mature cathepsin H by its own propeptide.


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References

Baudys, M., Meloun, B., Gan-Erdene, T., Fusek, M., Mares, M., Kostka, V., Pohl, J., and Blake, C.C. (1991). S–S bridges of cathepsin B and H from bovine spleen: a basis for cathepsin B model building and possible functional implications for discrimination between exo- and endopeptidase activities among cathepsins B, H and L. Biomed. Biochim. Acta 50, 569–577.Search in Google Scholar

Carmona, E., Dufour, E., Plouffe, C., Takebe, S., Mason, P., Mort, J.S., and Menard, R. (1996). Potency and selectivity of the cathepsin L propeptide as an inhibitor of cysteine proteases. Biochemistry 35, 8149–8157.10.1021/bi952736sSearch in Google Scholar

Chagas, J.R., Ferrer-Di Martino, M., Gauthier, F., and Lalmanach, G. (1996). Inhibition of cathepsin B by its propeptide: use of overlapping peptides to identify a critical segment. FEBS Lett. 392, 233–236.10.1016/0014-5793(96)00822-8Search in Google Scholar

Chen, Y., Plouffe, C., Menard, R., and Storer, A.C. (1996). Delineating functionally important regions and residues in the cathepsin B propeptide for inhibitory activity. FEBS Lett. 393, 24–26.10.1016/0014-5793(96)00847-2Search in Google Scholar

Cirman, T., Oresic, K., Droga-Mazovec, G., Turk, V., Reed, J.C., Myers, R.M., Salvesen, G.S., and Turk, B. (2004) Selective disruption of lysosomes in HeLa cells triggers apoptosis, mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins. J. Biol. Chem. 279, 3578–3587.Search in Google Scholar

Cygler, M., Sivaraman, J., Grochulski, P., Coulombe, R., Storer, A.C., and Mort, J.S. (1996). Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion. Structure 4, 405–416.10.1016/S0969-2126(96)00046-9Search in Google Scholar

del Re, E.C., Shuja, S., Cai, J., and Murnane, M.J. (2000). Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas. Br. J. Cancer 82, 1317–1326.10.1054/bjoc.1999.1098Search in Google Scholar

Delaria, K., Fiorentino, L., Wallace, L., Tamburini, P., Brownell, E., and Muller, D. (1994). Inhibition of cathepsin L-like cysteine proteases by cytotoxic T-lymphocyte antigen-2β. J. Biol. Chem. 269, 25172–25177.10.1016/S0021-9258(17)31513-2Search in Google Scholar

Dixon, M. (1953). The determination of enzyme inhibitor constants. Biochem. J. 55, 170–171.10.1042/bj0550170Search in Google Scholar

Dodt, J. and Reichwein, J. (2003). Human cathepsin H: deletion of the mini-chain switches substrate specificity from aminopeptidase to endopeptidase. Biol. Chem. 384, 1327–1332.10.1515/BC.2003.149Search in Google Scholar

Fox, T., de Miguel, E., Mort, J.S., and Storer, A.C. (1992). Potent slow-binding inhibition of cathepsin B by its propeptide. Biochemistry 31, 12571–12576.10.1021/bi00165a005Search in Google Scholar

Groves, M.R., Coulombe, R., Jenkins, J., and Cygler, M. (1998). Structural basis for specificity of papain-like cysteine protease proregions toward their cognate enzymes. Proteins 32, 504–514.10.1002/(SICI)1097-0134(19980901)32:4<504::AID-PROT8>3.0.CO;2-FSearch in Google Scholar

Guay, J., Falgueyret, J.P., Ducret, A., Percival, M.D., and Mancini J.A. (2000). Potency and selectivity of inhibition of cathepsin K, L and S by their respective propeptides. Eur. J. Biochem. 267, 6311–6318.10.1046/j.1432-1327.2000.01730.xSearch in Google Scholar

Guex, N. and Peitsch, M.C. (1997). SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18, 2714–2723.10.1002/elps.1150181505Search in Google Scholar

Guncar, G., Podobnik, M., Pungercar, J., Strukelj, B., Turk, V., and Turk, D. (1998). Crystal structure of porcine cathepsin H determined at 2.1 Å resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function. Structure 6, 51–61.10.1016/S0969-2126(98)00007-0Search in Google Scholar

Jenko, S., Dolenc, I., Guncar, G., Dobersek, A, Podobnik, M., and Turk, D. (2003). Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases. J. Mol. Biol. 326, 875–885.10.1016/S0022-2836(02)01432-8Search in Google Scholar

Karrer, K.M., Peiffer, S.L., and DiTomas, M.E. (1993). Two distinct gene subfamilies within the family of cysteine protease genes. Proc. Natl. Acad. Sci. USA 90, 3063–3067.10.1073/pnas.90.7.3063Search in Google Scholar

Koga, H., Mori, N., Yamada, H., Nishimura, Y., Tokuda, K., Kato, K., and Imoto, T. (1992). Endo- and aminopeptidase activities of rat cathepsin H. Chem. Pharm. Bull. (Tokyo) 40, 965–970.10.1248/cpb.40.965Search in Google Scholar

Kos, J., Stabuc, B., Schweiger, A., Krasovec, M., Cimerman, N., Kopitar-Jerala, N., and Vrhovec, I. (1997). Cathepsins B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clin. Cancer Res. 3, 1815–1822.Search in Google Scholar

Kurata, M., Yamamoto, Y., Watabe, S., Makino, Y., Ogawa, K., and Takahashi, S.Y. (2001). Bombyx cysteine proteinase inhibitor (BCPI) homologous to propeptide regions of cysteine proteinases is a strong, selective inhibitor of cathepsin L-like cysteine proteinases. J. Biochem. (Tokyo) 130, 857–863.10.1093/oxfordjournals.jbchem.a003058Search in Google Scholar

Lalmanach, G., Lecaille, F., Chagas, J.R., Authie, E., Scharfstein, J., Juliano, M.A., and Gauthier, F. (1998). Inhibition of trypanosomal cysteine proteinases by their propeptides. J. Biol. Chem. 273, 25112–25116.10.1074/jbc.273.39.25112Search in Google Scholar

Lazo, N.D. and Downing, D.T. (1997). Circular dichroism of model peptides emulating the amphipathic α-helical regionsof intermediate filaments. Biochemistry 36, 2559–2565.10.1021/bi963061bSearch in Google Scholar

Mach, L., Mort, J.S., and Glossl, J. (1994). Noncovalent complexes between the lysosomal proteinase cathepsin B and its propeptide account for stable, extracellular, high molecular mass forms of the enzyme. J. Biol. Chem. 269, 13036–13040.10.1016/S0021-9258(18)99980-1Search in Google Scholar

Ponder, J.W. and Case, D.A. (2003). Force fields for proteinsimulations. Adv. Prot. Chem. 66, 27–85.Search in Google Scholar

Ritonja, A., Popovic, T., Kotnik, M., Machleidt, W., and Turk, V. (1988). Amino acid sequences of the human kidney cathepsins H and L. FEBS Lett. 228, 341–545.10.1016/0014-5793(88)80028-0Search in Google Scholar

Rothe, M., Zichner, A., Auerswald, E.A., and Dodt, J. (1994). Structure/function implications for the aminopeptidase specificity of aleurain. Eur. J. Biochem. 224, 559–565.10.1111/j.1432-1033.1994.00559.xSearch in Google Scholar

Takahashi, T., Dehdarani, A.H., and Tang, J. (1988). Porcine spleen cathepsin H hydrolyzes oligopeptides solely by aminopeptidase activity. J. Biol. Chem. 263, 10952–10957.10.1016/S0021-9258(18)38062-1Search in Google Scholar

Tao, K., Stearns, N.A., Dong, J., Wu, Q.L., and Sahagian, G.G. (1994). The proregion of cathepsin L is required for proper folding, stability, and ER exit. Arch. Biochem. Biophys. 311, 19–27.10.1006/abbi.1994.1203Search in Google Scholar PubMed

Ueno, T., Linder, S., Na, C.L., Rice, W.R., Johansson, J., and Weaver, T.E. (2004). Processing of pulmonary surfactant protein B by napsin and cathepsin H. J. Biol. Chem. 279, 16178–16184.10.1074/jbc.M312029200Search in Google Scholar PubMed

Vasiljeva, O., Dolinar, M., Turk, V., and Turk, B. (2003). Recombinant human cathepsin H lacking the mini chain is an endopeptidase. Biochemistry 42, 13522–13528.10.1021/bi035355kSearch in Google Scholar PubMed

Vernet, T., Berti, P.J., de Montigny, C., Musil, R., Tessier, D.C., Menard, R., Magny, M.C., Storer, A.C., and Thomas, D.Y. (1995). 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. 270, 10838–10846.10.1074/jbc.270.18.10838Search in Google Scholar PubMed

Waghray, A., Keppler, D., Sloane, B.F., Schuger, L., and Chen, Y.Q. (2002). Analysis of a truncated form of cathepsin Hin human prostate tumor cells. J. Biol. Chem. 277, 11533–11538.10.1074/jbc.M109557200Search in Google Scholar PubMed

Wiederanders, B., Kaulmann, G., and Schilling, K. (2003). Functions of propeptide parts in cysteine proteases. Curr. Protein Pept. Sci. 4, 309–326.10.2174/1389203033487081Search in Google Scholar PubMed

Received: 2005-5-11
Accepted: 2005-6-22
Published Online: 2005-9-9
Published in Print: 2005-9-1

©2005 by Walter de Gruyter Berlin New York

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