Insights from Bacterial Subtilases into the Mechanisms of Intramolecular Chaperone-Mediated Activation of Furin

Methods in Molecular Biology

Volumn 768, Issue , 2011, Pages 59-106

  Shinde, Ujwal ^a   Thomas, Gary ^b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

histidine protonation; Intramolecular chaperones; pH sensors; proprotein convertases; protease activation and regulation; secretory pathway; subtilases

Indexed keywords

BACTERIAL PROTEIN; CHAPERONE; ENZYME PRECURSOR; FURIN; SUBTILISIN;

ARTICLE; BACILLUS; CHEMICAL STRUCTURE; ENZYME ACTIVATION; HUMAN; METABOLISM; PHYSIOLOGY; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN PROCESSING; SECRETORY PATHWAY; THERMODYNAMICS; ULTRASTRUCTURE;

BACILLUS; BACTERIAL PROTEINS; ENZYME ACTIVATION; ENZYME PRECURSORS; FURIN; HUMANS; MODELS, MOLECULAR; MOLECULAR CHAPERONES; PROTEIN BINDING; PROTEIN FOLDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; SECRETORY PATHWAY; SUBTILISINS; THERMODYNAMICS;

BACTERIA (MICROORGANISMS); EUKARYOTA; PROKARYOTA;

EID: 80054733266     PISSN: 10643745     EISSN: 19406029     Source Type: Book Series    
DOI: 10.1007/978-1-61779-204-5_4     Document Type: Chapter

References (127)

1. Nakayama, K. (1997) Furin: A mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins Biochem J 327(Pt 3), 625–35.
2. Thomas, G. (2002) Furin at the cutting edge: From protein traffic to embryogenesis and disease Nat Rev Mol Cell Biol 3, 753–66.
3. Fuller, R. S., Brake, A., and Thorner, J. (1989) Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease Proc Natl Acad Sci USA 86, 1434–8.
4. Fuller, R. S., Brake, A. J., and Thorner, J. (1989) Intracellular targeting and structural conservation of a prohormone-processing endoprotease Science 246, 482–6.
5. Fuller, R. S., Sterne, R. E., and Thorner, J. (1988) Enzymes required for yeast prohormone processing Annu Rev Physiol 50, 345–62.
6. Thomas, G., Thorne, B. A., Thomas., L. et al. (1988) Yeast KEX2 endopeptidase correctly cleaves a neuroendocrine prohormone in mammalian cells Science 241, 226–30.
7. Bergeron, F., Leduc, R., and Day, R. (2000) Subtilase-like pro-protein convertases: From molecular specificity to therapeutic applications J Mol Endocrinol 24, 1–22.
8. Seidah, N. G., Benjannet, S., Wickham, L. et al. (2003) The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neu- ronal differentiation Proc Natl Acad Sci USA 100, 928–33.
9. Seidah, N. G., Mowla, S. J., Hamelin, J. et al. (1999) Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization Proc Natl Acad Sci USA 96, 1321–6.
10. Toure, B. B., Munzer, J. S., Basak, A. et al. (2000) Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment J Biol Chem 275, 2349–58.
11. Seidah, N. G., Mayer, G., Zaid, A. et al. (2008) The activation and physiological functions of the proprotein convertases Int J Biochem Cell Biol 40, 1111–25.
12. Lambert, G., Charlton, F., Rye, K. A., and Piper, D. E. (2009) Molecular basis of PCSK9 function Atherosclerosis 203, 1–7.
13. Siezen, R. J., and Leunissen, J. A. (1997) Subtilases: The superfamily of subtilisin-like serine proteases Protein Sci 6, 501–23.
14. Rawlings, N. D., Barrett, A. J., and Bateman, A. (2009) MEROPS: The peptidase database Nucleic Acids Res 38, D227–33.
15. Smith, E. L., Markland, F. S., Kasper, C. B., DeLange, R. J., Landon, M., and Evans, W. H. (1966) The complete amino acid sequence of two types of subtilisin, BPN’ and Carlsberg J Biol Chem 241, 5974–6.
16. Wright, C. S., Alden, R. A., and Kraut, J. (1969) Structure of subtilisin BPN’ at 2.5 angstrom resolution Nature 221, 235–42.
17. Bryan, P. N. (2000) Protein engineering of subtilisin Biochim Biophys Acta 1543, 203–22.
18. Lipkind, G., Gong, Q., and Steiner, D. F. (1995) Molecular modeling of the substrate specificity of prohormone convertases SPC2 and SPC3 J Biol Chem 270, 13277–84.
19. Oliva, A. A., Jr., Steiner, D. F., and Chan, S. J. (1995) Proprotein convertases in amphioxus: Predicted structure and expression of proteases SPC2 and SPC3 Proc Natl Acad Sci USA 92, 3591–5.
20. Henrich, S., Cameron, A., Bourenkov, G. P. et al. (2003) The crystal structure of the proprotein processing proteinase furin explains its stringent specificity Nat Struct Biol 10, 520–6.
21. Holyoak, T., Wilson, M. A., Fenn, T. D. et al. (2003) 2.4 A resolution crystal structure of the prototypical hormone-processing protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitor Biochemistry 42, 6709–18.
22. Henrich, S., Lindberg, I., Bode, W., and Than, M. E. (2005) Proprotein convertase models based on the crystal structures of furin and kexin: Explanation of their specificity J Mol Biol 345, 211–27.
23. Demaurex, N. (2002) pH Homeostasis of cellular organelles News Physiol Sci 17, 1–5.
24. Casey, J. R., Grinstein, S., and Orlowski, J. (2010) Sensors and regulators of intracellular pH Nat Rev Mol Cell Biol 11, 50–61.
25. Anderson, E. D., Molloy, S. S., Jean, F., Fei, H., Shimamura, S., and Thomas, G. (2002) The ordered and compartment-specific auto-proteolytic removal of the furin intramolecular chaperone is required for enzyme activation J Biol Chem 277, 12879–90.
26. Feliciangeli, S. F., Thomas, L., Scott, G. K. et al. (2006) Identification of a pH sensor in the furin propeptide that regulates enzyme activation J Biol Chem 281, 16108–16.
27. Ehrmann, M., and Clausen, T. (2004) Proteolysis as a regulatory mechanism Annu Rev Genet 38, 709–24.
28. Anderson, E. D., VanSlyke, J. K., Thulin, C. D., Jean, F., and Thomas, G. (1997) Activation of the furin endoprotease is a multiple-step process: Requirements for acidification and internal propeptide cleavage EMBO J 16, 1508–18.
29. Shinde, U., and Inouye, M. (2000) Intramolecular chaperones: Polypeptide extensions that modulate protein folding Semin Cell Dev Biol 11, 35–44.
30. Ikemura, H., Takagi, H., and Inouye, M. (1987) Requirement of pro-sequence for the production of active subtilisin E in Escherichia coli J Biol Chem 262, 7859–64.
31. Ikemura, H., and Inouye, M. (1988) In vitro processing of pro-subtilisin produced in Escherichia coli J Biol Chem 263, 12959–63.
32. Zhu, X. L., Ohta, Y., Jordan, F., and Inouye, M. (1989) Pro-sequence of subtilisin can guide the refolding of denatured subtilisin in an intermolecular process Nature 339, 483–4.
33. Shinde, U., Fu, X., and Inouye, M. (1999) A pathway for conformational diversity in proteins mediated by intramolecular chaperones J Biol Chem 274, 15615–21.
34. Yabuta, Y., Takagi, H., Inouye, M., and Shinde, U. (2001) Folding pathway mediated by an intramolecular chaperone: Propeptide release modulates activation precision of pro-subtilisin J Biol Chem 276, 44427–34.
35. Ohta, Y., Hojo, H., Aimoto, S. et al. (1991) Pro-peptide as an intramolecular chaperone: Renaturation of denatured subtilisin E with a synthetic pro-peptide [corrected] Mol Microbiol 5, 1507–10.
36. Ohta, Y., and Inouye, M. (1990) Pro-subtilisin E: Purification and characterization of its autoprocessing to active subtilisin E in vitro Mol Microbiol 4, 295–304.
37. Eder, J., and Fersht, A. R. (1995) Pro-sequence-assisted protein folding Mol Microbiol 16, 609–14.
38. Shinde, U., and Inouye, M. (1993) Intramolecular chaperones and protein folding Trends Biochem Sci 18, 442–6.
39. Ellis, R. J. (1993) The general concept of molecular chaperones Philos Trans R Soc Lond B Biol Sci 339, 257–61.
40. Ellis, R. J. (2007) Protein misassembly: Macromolecular crowding and molecular chaperones Adv Exp Med Biol 594, 1–13.
41. Ellis, R. J., and van der Vies, S. M. (1991) Molecular chaperones Annu Rev Biochem 60, 321–47.
42. Shinde, U. P., Liu, J. J., and Inouye, M. (1997) Protein memory through altered folding mediated by intramolecular chaperones Nature 389, 520–2.
43. Chen, Y. J., and Inouye., M. (2008) The intramolecular chaperone-mediated protein folding Curr Opin Struct Biol 18, 765–70.
44. Silen, J. L., and Agard, D. A. (1989) The alpha-lytic protease pro-region does not require a physical linkage to activate the protease domain in vivo Nature 341, 462–4.
45. Baker, D., Sohl, J. L., and Agard, D. A. (1992) A protein-folding reaction under kinetic control Nature 356, 263–5.
46. Jaswal, S. S., Sohl, J. L., Davis, J. H., and Agard, D. A. (2002) Energetic landscape of alpha-lytic protease optimizes longevity through kinetic stability Nature 415, 343–6.
47. Valls, L. A., Hunter, C. P., Rothman, J. H., and Stevens, T. H. (1987) Protein sorting in yeast: The localization determinant of yeast vacuolar carboxypeptidase Y resides in the propeptide Cell 48, 887–97.
48. Ammerer, G., Hunter, C. P., Rothman, J. H., Saari, G. C., Valls, L. A., and Stevens, T. H. (1986) PEP4 gene of Saccharomyces cerevisiae encodes proteinase A, a vacuolar enzyme required for processing of vacuolar precursors Mol Cell Biol 6, 2490–9.
49. Ramos, C., Winther, J. R., and Kielland-Brandt, M. C. (1994) Requirement of the propeptide for in vivo formation of active yeast carboxypeptidase Y J Biol Chem 269, 7006–12.
50. Winther, J. R., and Sorensen, P. (1991) Propeptide of carboxypeptidase Y provides a chaperone-like function as well as inhibition of the enzymatic activity Proc Natl Acad Sci USA 88, 9330–4.
51. Winther, J. R., Sorensen, P., and Kielland-Brandt, M. C. (1994) Refolding of a carboxypeptidase Y folding intermediate in vitro by low-affinity binding of the proregion J Biol Chem 269, 22007–13.
52. van den Hazel, H. B., Kielland-Brandt, M. C., and Winther, J. R. (1993) The propeptide is required for in vivo formation of stable active yeast proteinase A and can function even when not covalently linked to the mature region J Biol Chem 268, 18002–7.
53. Smith, S. M., and Gottesman, M. M. (1989) Activity and deletion analysis of recombinant human cathepsin L expressed in Escherichia coli J Biol Chem 264, 20487–95.
54. Ogino, T., Kaji, T., Kawabata, M. et al. (1999) Function of the propeptide region in recombinant expression of active procathepsin L in Escherichia coli J Biochem (Tokyo) 126, 78–83.
55. Wiederanders, B., Kaulmann, G., and Schilling, K. (2003) Functions of propeptide parts in cysteine proteases Curr Protein Pept Sci 4, 309–26.
56. Hou, W. S., Bromme, D., Zhao, Y. et al. (1999) Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis J Clin Invest 103, 731–8.
57. Schulz, E. C., Neumann, P., Gerardy-Schahn, R., Sheldrick, G. M., and Ficner, R. (2010) Structure analysis of endosialidase NF at 0.98 A resolution Acta Crystallogr D Biol Crystallogr 66, 176–80.
58. Schulz, E. C., Schwarzer, D., Frank, M. et al. (2010) Structural basis for the recognition and cleavage of polysialic acid by the bacteriophage K1F tailspike protein EndoNF J Mol Biol 397, 341–51.
59. McIver, K. S., Kessler, E., and Ohman, D. E. (2004) Identification of residues in the Pseudomonas aeruginosa elastase propeptide required for chaperone and secretion activities Microbiology 150, 3969–77.
60. Tang, B., Nirasawa, S., Kitaoka, M., Marie-Claire, C., and Hayashi, K. (2003) General function of N-terminal propeptide on assisting protein folding and inhibiting catalytic activity based on observations with a chimeric thermolysin-like protease Biochem Biophys Res Commun 301, 1093–8.
61. Gray, T. E., Eder, J., Bycroft, M., Day, A. G., and Fersht, A. R. (1993) Refolding of barnase mutants and pro-barnase in the presence and absence of GroEL EMBO J 12, 4145–50.
62. Suter, U., Heymach, J. V., Jr., and Shooter, E. M. (1991) Two conserved domains in the NGF propeptide are necessary and sufficient for the biosynthesis of correctly processed and biologically active NGF EMBO J 10, 2395–400.
63. Thorne, B. A., and Plowman, G. D. (1994) The heparin-binding domain of amphireg-ulin necessitates the precursor pro-region for growth factor secretion Mol Cell Biol 14, 1635–46.
64. Steiner, D. F. (2004) The proinsulin C-peptide–a multirole model Exp Diabesity Res 5, 7–14.
65. Voorberg, J., Fontijn, R., Calafat, J., Janssen, H., van Mourik, J. A., and Pannekoek, H. (1993) Biogenesis of von Willebrand factor-containing organelles in heterologous transfected CV-1 cells EMBO J 12, 749–58.
66. Weissman, J. S., and Kim, P. S. (1992) The pro region of BPTI facilitates folding Cell 71, 841–51.
67. Morgunova, E., Tuuttila, A., Bergmann, U. et al. (1999) Structure of human pro-matrix metalloproteinase-2: Activation mechanism revealed Science 284, 1667–70.
68. Baker, D., Shiau, A. K., and Agard, D. A. (1993) The role of pro regions in protein folding Curr Opin Cell Biol 5, 966–70.
69. Baker, D., and Agard, D. A. (1994) Kinetics versus thermodynamics in protein folding Biochemistry 33, 7505–9.
70. Shinde, U., and Inouye, M. (1994) The structural and functional organization of intramolecular chaperones: The N-terminal propeptides which mediate protein folding J Biochem (Tokyo) 115, 629–36.
71. Kojima, S., Iwahara, A., and Yanai, H. (2005) Inhibitor-assisted refolding of protease: A protease inhibitor as an intramolecular chaperone FEBS Lett 579, 4430–6.
72. Yabuta, Y., Subbian, E., Oiry, C., and Shinde, U. (2003) Folding pathway mediated by an intramolecular chaperone. A functional peptide chaperone designed using sequence databases J Biol Chem 278, 15246–51.
73. Li, Y., Hu, Z., Jordan, F., and Inouye, M. (1995) Functional analysis of the propeptide of subtilisin E as an intramolecular chaperone for protein folding. Refolding and inhibitory abilities of propeptide mutants J Biol Chem 270, 25127–32.
74. Kobayashi, T., and Inouye, M. (1992) Functional analysis of the intramolecular chaperone. Mutational hot spots in the subtilisin pro-peptide and a second-site suppressor mutation within the subtilisin molecule J Mol Biol 226, 931–3.
75. Buevich, A. V., Shinde, U. P., Inouye, M., and Baum, J. (2001) Backbone dynamics of the natively unfolded pro-peptide of subtilisin by heteronuclear NMR relaxation studies J Biomol NMR 20, 233–49.
76. Jain, S. C., Shinde, U., Li, Y., Inouye, M., and Berman, H. M. (1998) The crystal structure of an autoprocessed Ser221Cys-subtilisin E-propeptide complex at 2.0 A resolution J Mol Biol 284, 137–44.
77. Shinde, U., and Inouye, M. (1995b) Folding pathway mediated by an intramolecular chaperone: Characterization of the structural changes in pro-subtilisin E coincident with autoprocessing J Mol Biol 252, 25–30.
78. Shinde, U., Li, Y., Chatterjee, S., and Inouye, M. (1993) Folding pathway mediated by an intramolecular chaperone Proc Natl Acad Sci USA 90, 6924–8.
79. Ruan, B., Hoskins, J., and Bryan, P. N. (1999) Rapid folding of calcium-free subtilisin by a stabilized pro-domain mutant Biochemistry 38, 8562–71.
80. Ruan, B., Hoskins, J., Wang, L., and Bryan, P. N. (1998) Stabilizing the subtilisin BPN’ pro-domain by phage display selection: How restrictive is the amino acid code for maximum protein stability? Protein Sci 7, 2345–53.
81. Marie-Claire, C., Yabuta, Y., Suefuji, K., Matsuzawa, H., and Shinde, U. (2001) Folding pathway mediated by an intramolecular chaperone: The structural and functional characterization of the aqualysin I propeptide J Mol Biol 305, 151–65.
82. Gallagher, T., Gilliland, G., Wang, L., and Bryan, P. (1995) The prosegment-subtilisin BPN’ complex: Crystal structure of a specific ‘foldase’ Structure 3, 907–14.
83. Radisky, E. S., King, D. S., Kwan, G., and Koshland, D. E., Jr. (2003) The role of the protein core in the inhibitory power of the classic serine protease inhibitor, chymotrypsin inhibitor 2 Biochemistry 42, 6484–92.
84. Alexander, P. A., Ruan, B., and Bryan, P. N. (2001) Cation-dependent stability of subtilisin Biochemistry 40, 10634–9.
85. Yabuta, Y., Subbian, E., Takagi, H., Shinde, U., and Inouye, M. (2002) Folding pathway mediated by an intramolecular chaperone: Dissecting conformational changes coincident with autoprocessing and the role of Ca(2+) in subtilisin maturation J Biochem (Tokyo) 131, 31–7.
86. Inouye, M., Fu, X., and Shinde, U. (2001) Substrate-induced activation of a trapped IMC-mediated protein folding intermediate Nat Struct Biol 8, 321–5.
87. Shinde, U., and Inouye, M. (1995a) Folding mediated by an intramolecular chaperone: Autoprocessing pathway of the precursor resolved via a substrate assisted catalysis mechanism J Mol Biol 247, 390–5.
88. Bryan, P., Wang, L., Hoskins, J. et al. (1995) Catalysis of a protein folding reaction: Mechanistic implications of the 2.0 A structure of the subtilisin-prodomain complex Biochemistry 34, 10310–18.
89. Li, Y., and Inouye, M. (1996) The mechanism of autoprocessing of the propeptide of prosubtilisin E: Intramolecular or intermolecular event? J Mol Biol 262, 591–4.
90. Comellas-Bigler, M., Maskos, K., Huber, R., Oyama, H., Oda, K., and Bode, W. (2004) 1.2 A crystal structure of the serine carboxyl proteinase pro-kumamolisin; structure of an intact pro-subtilase Structure (Camb) 12, 1313–23.
91. Eder, J., Rheinnecker, M., and Fersht, A. R. (1993) Folding of subtilisin BPN’: Characterization of a folding intermediate Biochemistry 32, 18–26.
92. Kuwajima, K. (1989) The molten globule state as a clue for understanding the folding and cooperativity of globular-protein structure Proteins 6, 87–103.
93. Eder, J., Rheinnecker, M., and Fersht, A. R. (1993) Folding of subtilisin BPN’: Role of the pro-sequence J Mol Biol 233, 293–304.
94. Bryan, P., Alexander, P., Strausberg, S. et al. (1992) Energetics of folding subtilisin BPN’ Biochemistry 31, 4937–45.
95. Sohl, J. L., Jaswal, S. S., and Agard, D. A. (1998) Unfolded conformations of alpha-lytic protease are more stable than its native state Nature 395, 817–19.
96. Alexander, P. A., Ruan, B., Strausberg, S. L., and Bryan, P. N. (2001) Stabilizing mutations and calcium-dependent stability of subtilisin Biochemistry 40, 10640–4.
97. Almog, O., Gallagher, T., Tordova, M., Hoskins, J., Bryan, P., and Gilliland, G. L. (1998) Crystal structure of calcium-independent subtilisin BPN’ with restored thermal stability folded without the prodomain Proteins 31, 21–32.
98. Wang, L., Ruan, B., Ruvinov, S., and Bryan, P. N. (1998) Engineering the independent folding of the subtilisin BPN’ pro-domain: Correlation of pro-domain stability with the rate of subtilisin folding Biochemistry 37, 3165–71.
99. Ruvinov, S., Wang, L., Ruan, B. et al. (1997) Engineering the independent folding of the subtilisin BPN’ prodomain: Analysis of two-state folding versus protein stability Biochemistry 36, 10414–21.
100. Fu, X., Inouye, M., and Shinde, U. (2000) Folding pathway mediated by an intramolecular chaperone. The inhibitory and chaperone functions of the subtilisin propeptide are not obligatorily linked J Biol Chem 275, 16871–8.
101. Shastry, M. C., and Udgaonkar, J. B. (1995) The folding mechanism of barstar: Evidence for multiple pathways and multiple intermediates J Mol Biol 247, 1013–27.
102. Hayashi, T., Matsubara, M., Nohara, D., Kojima, S., Miura, K., and Sakai, T. (1994) Renaturation of the mature subtilisin BPN’ immobilized on agarose beads FEBS Lett 350, 109–12.
103. Matsubara, M., Kurimoto, E., Kojima, S., Miura, K., and Sakai, T. (1994) Achievement of renaturation of subtilisin BPN’ by a novel procedure using organic salts and a digestible mutant of Streptomyces subtilisin inhibitor FEBS Lett 342, 193–6.
104. Yabuta, Y., Subbian, E., Takagi, H., Shinde, U., and Inouye, M. (2002) Folding pathway mediated by an intramolecular chaperone: Dissecting conformational changes coincident with autoprocessing and the role of Ca(2+) in subtilisin maturation J Biochem 131, 31–7.
105. Anfinsen, C. B. (1973) Principles that govern the folding of protein chains Science 181, 223–30.
106. Karplus, M. (1997) The Levinthal paradox: Yesterday and today Fold Des 2, S69–75.
107. Franke, A. E., Danley, D. E., Kaczmarek, F. S. et al. (1990) Expression of human plasminogen activator inhibitor type-1 (PAI-1) in Escherichia coli as a soluble protein comprised of active and latent forms. Isolation and crystallization of latent PAI-1 Biochim Biophys Acta 1037, 16–23.
108. Huntington, J. A., Pannu, N. S., Hazes, B., Read, R. J., Lomas, D. A., and Carrell, R. W. (1999) A 2.6 A structure of a serpin polymer and implications for conformational disease J Mol Biol 293, 449–55.
109. Huntington, J. A., Read, R. J., and Carrell, R. W. (2000) Structure of a serpin-protease complex shows inhibition by deformation Nature 407, 923–6.
110. Subbian, E., Yabuta, Y., and Shinde, U. P. (2005) Folding pathway mediated by an intramolecular chaperone: Intrinsically unstructured propeptide modulates stochastic activation of subtilisin J Mol Biol 347, 367–83.
111. Subbian, E., Yabuta, Y., and Shinde, U. (2004) Positive selection dictates the choice between kinetic and thermodynamic protein folding and stability in subtilases Biochemistry 43, 14348–60.
112. Bryan, P. N. (2002) Prodomains and protein folding catalysis Chem Rev 102, 4805–16.
113. Siezen, R. J. (1996) Subtilases: Subtilisin-like serine proteases Adv Exp Med Biol 379, 75–93.
114. Tangrea, M. A., Bryan, P. N., Sari, N., and Orban, J. (2002) Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus J Mol Biol 320, 801–12.
115. Tangrea, M. A., Alexander, P., Bryan, P. N., Eisenstein, E., Toedt, J., and Orban, J. (2001) Stability and global fold of the mouse prohormone convertase 1 pro-domain Biochemistry 40, 5488–95.
116. Nour, N., Basak, A., Chretien, M., and Seidah, N. G. (2003) Structure-function analysis of the prosegment of the proprotein convertase PC5A J Biol Chem 278, 2886–95.
117. Nour, N., Mayer, G., Mort, J. S. et al. (2005) The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases Mol Biol Cell 16, 5215–26.
118. Dikeakos, J. D., Lacombe, M. J., Mercure, C., Mireuta, M., and Reudelhuber, T. L. (2007) A hydrophobic patch in a charged alpha-helix is sufficient to target proteins to dense core secretory granules J Biol Chem 282, 1136–43.
119. Malfait, A. M., Arner, E. C., Song, R. H. et al. (2008) Proprotein convertase activation of aggrecanases in cartilage in situ Arch Biochem Biophys 478, 43–51.
120. Jutras, I., Seidah, N. G., Reudelhuber, T. L., and Brechler, V. (1997) Two activation states of the prohormone convertase PC1 in the secretory pathway J Biol Chem 272, 15184–8.
121. Leduc, R., Molloy, S. S., Thorne, B. A., and Thomas, G. (1992) Activation of human furin precursor processing endoprotease occurs by an intramolecular autoprote-olytic cleavage J Biol Chem 267, 14304–8.
122. Wan, L., Molloy, S. S., Thomas, L. et al. (1998) PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization Cell 94, 205–16.
123. Kucerova, H., and Chaloupka, J. (1995) Intracellular serine proteinase behaves as a heat-stress protein in nongrowing but as a cold-stress protein in growing populations of Bacillus megaterium Curr Microbiol 31, 39–43.
124. Kucerova, H., Hlavacek, O., Vachova, L., Mlichova, S., and Chaloupka, J. (2001) Differences in the regulation of the intracellular Ca2+-dependent serine proteinase activity between Bacillus subtilis and B. megaterium Curr Microbiol 42, 178–83.
125. Vachova, L. (1996) Activation of the intracellular Ca(2+)-dependent serine protease ISP1 of bacillus megaterium by purification or by high Ca2+ concentrations Biochem Mol Biol Int 40, 947–54.
126. Vachova, L., Kucerova, H., Benesova, J., and Chaloupka, J. (1994) Heat and osmotic stress enhance the development of cytoplasmic serine proteinase activity in sporulating Bacillus megaterium Biochem Mol Biol Int 32, 1049–57.
127. Weisz, O. A. (2003) Organelle acidification and disease Traffic 4, 57–64.