Purification and characterization of the human γ-secretase complex

Biochemistry

Volumn 43, Issue 30, 2004, Pages 9774-9789

  Fraering, Patrick C ^a   Ye, Wenjuan ^a   Strub, Jean Marc ^b   Dolios, Georgia ^c   LaVoie, Matthew J ^a   Ostaszewski, Beth L ^a   Van Dorsselaer, Alain ^b   Wang, Rong ^c   Selkoe, Dennis J ^a   Wolfe, Michael S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MEMBRANES; CATALYSIS; CONCENTRATION (PROCESS); CONFORMATIONS; ENZYMES; MASS SPECTROMETRY; PURIFICATION; SUBSTRATES; TOXIC MATERIALS;

GENETIC STUDIES; INTRAMEMBRANES; NEUROTOXINS;

BIOCHEMISTRY;

AMYLOID BETA PRECURSOR PROTEIN; AMYLOID BETA PROTEIN; ANTERIOR PHARYNX DEFECTIVE 1 PROTEIN; GAMMA SECRETASE; MEMBRANE PROTEIN; NICASTRIN; NOTCH RECEPTOR; PEN 2 PROTEIN; PHOSPHATIDYLCHOLINE; PRESENILIN; PROTEIN; PROTEINASE; SPHINGOMYELIN; SULINDAC SULFIDE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL CELL; ARTICLE; CHO CELL; CONTROLLED STUDY; DROSOPHILA; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME CONFORMATION; ENZYME PURIFICATION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; MASS SPECTROMETRY; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL;

AMINO ACID SEQUENCE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ENDOPEPTIDASES; CHO CELLS; CRICETINAE; ENDOPEPTIDASES; GAMMA-AMINOBUTYRIC ACID; HUMANS; HYDROLYSIS; KINETICS; LIPIDS; MACROMOLECULAR SUBSTANCES; MASS SPECTROMETRY; MEMBRANE GLYCOPROTEINS; MEMBRANE PROTEINS; MICE; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PEPTIDES; PRESENILIN-1; PROTEASE INHIBITORS; RECEPTORS, NOTCH; SODIUM DODECYL SULFATE; SUBSTRATE SPECIFICITY; SULINDAC; TRIGLYCERIDES;

ANIMALIA; MAMMALIA;

EID: 3342993335     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi0494976     Document Type: Article

References (70)

1. Selkoe, D. (2001) Alzheimer's Disease: Genes, Proteins, and Therapy, Physiol. Rev. 81, 741-66.
2. Vassar, R., and Citron, M. (2000) Abeta-generating enzymes: recent advances in β- and γ-secretase research, Neuron 27, 419-22.
3. Wolfe, M. S., De Los Angeles, J., Miller, D. D., Xia, W., and Selkoe, D. J. (1999) Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease, Biochemistry 38, 11223-30.
4. Wolfe, M. S., and Selkoe, D. (2002) Biochemistry. Intramembrane proteases-mixing oil and water, Science 296, 2156-7.
5. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Gundula, G., Annaert, W., Von Figura, K., and Van Leuven, F. (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein, Nature 391, 387-90.
6. Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity, Nature 398, 513-7.
7. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., Goate, A., and Kopan, R. (1999) A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain, Nature 398, 518-22.
8. Struhl, G., and Greenwald, I. (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila, Nature 398, 522-5.
9. Ye, Y., Lukinova, N., and Fortini, M. E. (1999) Neurogenic phenotypes and altered Notch processing in Drosophila presenilin mutants, Nature 398, 525-9.
10. Francis, R., McGrath, G., Zhang, J., Ruddy, D. A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M. C., Parks, A. L., Xu, W., Li, J., Gurney, M., Myers, R. L., Himes, C. S., Hiebsch, R., Ruble, C., Nye, J. S., and Curtis, D. (2002) aph-1 and pen-2 are required for Notch pathway signaling, γ-secretase cleavage of βAPP, and presenilin protein accumulation, Dev. Cell 3, 85-97.
11. Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G., and Iwatsubo, T. (2003) The role of presenilin cofactors in the γ-secretase complex, Nature 422, 438-41.
12. Kimberly, W. T., LaVoie, M., Ostaszewski, B. L., Ye, W., Wolfe, M. S., and Selkoe, D. J. (2003) γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2, Proc. Natl. Acad. Sci. U.S.A. 100, 6382-7.
13. Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H., and Haass, C. (2003) Reconstitution of γ-secretase activity, Nat. Cell Biol. 5, 486-8.
14. Wolfe, M. (2002) Therapeutic strategies for Alzheimer's disease, Nat. Rev. Drug Discov. 1, 859-66.
15. Edbauer, D., Winkler, E., Haass, C., and Steiner, H. (2002) Presenilin and nicastrin regulate each other and determine amyloid β-peptide production via complex formation, Proc. Natl. Acad. Sci. U.S.A. 99, 8666-71.
16. Farmery, M. R., Tjernberg, L., Pursglove, S. E., Bergman, A., Winblad, B., and Naslund, J. (2003) Partial purification and characterization of γ-secretase from post-mortem human brain, J. Biol. Chem. 278, 24277-84.
17. Nyabi, O., Bentahir, M., Horre, K., Herreman, A., Gottardi-Littell, N., Van Broeckhoven, C., Merchiers, P., Spittaels, K., Annaert, W., and De Strooper, B. (2003) Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild-type presenilin, J. Biol. Chem. 278, 43430-6.
18. Ni, C. Y., Murphy, M., Golde, T. E., and Carpenter, G. (2001) γ-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase, Science 294, 2179-81.
19. Marambaud, P., Shioi, J., Serban, G., Georgakopoulos, A., Sarner, S., Nagy, V., Baki, L., Wen, P., Efthimiopoulos, S., Shao, Z., Wisniewski, T., and Robakis, N. K. (2001) A presenilin-1/γ-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions, EMBO J. 21, 1948-56.
20. Kim, D. Y., Ingano, L., and Kovacs, D. M. (2002) Nectin-1alpha, an immunoglobulin-like receptor involved in the formation of synapses, is a substrate for presenilin/γ-secretase-like cleavage, J. Biol. Chem. 277, 49976-81.
21. May, P., Reddy, Y., and Herz, J. (2002) Proteolytic processing of low-density lipoprotein receptor-related protein mediates regulated release of its intracellular domain, J. Biol. Chem. 277, 18736-43.
22. Lammich, S., Okochi, M., Takeda, M., Kaether, C., Capell, A., Zimmer, A. K., Edbauer, D., Walter, J., Steiner, H., and Haass, C. (2002) Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of its intracellular domain and the secretion of an Abeta-like peptide, J. Biol. Chem. 277, 44754-9.
23. LaVoie, M. J., and Selkoe, D. (2003) The Notch ligands, Jagged and Delta, are sequentially processed by α-secretase and presenilin/γ- secretase and release signaling fragments, J. Biol. Chem. 278, 34427-37.
24. Suzuki, N., Cheung, T., Cai, X. D., Odaka, A., Otvos, L., Jr., Eckman, C., Golde, T. E., and Younkin, S. G. (1994) An increased percentage of long amyloid β-protein secreted by familial amyloid β-protein precursor (β APP717) mutants, Science 264, 1336-40.
25. Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C. M., Kim, G., Seekins, S., Yager, D., Slunt, H. H., Wang, R., Seeger, M., Levey, A. I., Gandy, S. E., Copeland, N. G., Jenkins, N. A., Price, D. L., Younkin, S. G., and Sisodia, S. (1996) Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo, Neuron 17, 1005-13.
26. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C. M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M., Holcomb, L., Refolo, L., Zenk, B., Hardy, J., and Younkin S. (1996) Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1, Nature 383, 710-3.
27. Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., Larson, E., Levy-Lahad, E., Viitanen, M., Peskind, E., Poorkaj, P., Schellenberg, G., Tanzi, R., Wasco, W., Lannfelt, L., Selkoe, D., and Youkin, S. (1996) Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease, Nat. Med. 2, 864-70.
28. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A., Kholodenka, D., Motter, R., Sherrington, R., Perry, B., Yao, H., Strome, R., Lieberburg, I., Rommens, J., Kim, S., Schenk, D., Fraser, P., St. George-Hyslop, P., and Selkoe, D. J. (1997) Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice, Nat. Med. 3, 67-72.
29. Fraering, P. C., LaVoie, M., Ye, W., Ostaszewski, B. L., Kimberly, W. T., Selkoe, D. J., and Wolfe, M. S. (2004) Detergent-dependent dissociation of active γ-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex, Biochemistry 43, 323-33.
30. Kimberly, W. T., Esler, W., Ye, W., Ostaszewski, B. L., Gao, J., Diehl, T., Selkoe, D. J., and Wolfe, M. S. (2003) Notch and the amyloid precursor protein are cleaved by similar β-secretase(s), Biochemistry 42, 137-44.
31. Esler, W. P., Kimberly, W., Ostaszewski, B. L., Ye, W., Diehl, T. S., Selkoe, D. J., and Wolfe, M. S. (2002) Activity-dependent isolation of the presenilin-γ-secretase complex reveals nicastrin and a γ substrate, Proc. Natl. Acad. Sci. U.S.A. 99, 2720-5.
32. Li, Y. M., Lai, M., Xu, M., Huang, Q., DiMuzio-Mower, J., Sardana, M. K., Shi, X. P., Yin, K. C., Shafer, J. A., and Gardell, S. J. (2000) Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state, Proc. Natl. Acad. Sci. U.S.A. 97, 6138-43.
33. Xia, W., Zhang, J., Ostaszewski, B. L., Kimberly, W. T., Seubert, P., Koo, E. H., Shen, J., and Selkoe, D. J. (1998) Presenilin 1 regulates the processing of β-amyloid precursor protein C-terminal fragments and the generation of amyloid β-protein in endoplasmic reticulum and Golgi, Biochemistry 37, 16465-71.
34. Wang, R., Sweeney, D., Gandy, S. E., and Sisodia, S. S. (1996) The profile of soluble amyloid β-protein in cultured cell media. Detection and quantificaiton of amyloid β-protein and variants by immunoprecipitation- mass spectrometry, J. Biol. Chem. 271, 31894-31902.
35. LaVoie, M. J., Fraering, P. C., Ostaszewski, B. L., Ye, W., Kimberly, W. T., Wolfe, M. S., and Selkoe, D. J. (2003) Assembly of the γ-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin, J. Biol. Chem. 278, 37213-22.
36. Fujiki, Y., Hubbard, A. L., Fowler, S., and Lazarow, P. B. (1982) Isolation of intracellular membranes by means of sodium carbonate treatment: Application to endoplasmic reticulum, J. Cell Biol. 93, 97-102.
37. Capell, A., Grunberg, J., Pesold, B., Diehlmann, A., Citron, M., Nixon, R., Beyreuther, K., Selkoe, D. J., and Haass, C. (1998) The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150 kDa molecular mass complex, J. Biol. Chem. 273, 3205-11.
38. Yu, G., Chen, F., Levesque, G., Nishimura, M., Zhang, D. M., Levesque, L., Rogaeva, E., Xu, D., Liang, Y., Duthie, M., St. George-Hyslop, P. H., and Fraser, P. E. (1998) The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains β-catenin, J. Biol. Chem. 273, 16470-5.
39. Sahara, N., Yahagi, Y., Takagi, H., Kondo, T., Okochi, M., Usami, M., Shirasawa, T., and Mori, H. (1996) Identification and characterization of presenilin 1-467, 1-463, and 1-374, FEBS Lett. 381, 7-11.
40. Kimberly, W. T., LaVoie, M., Ostaszewski, B. L., Ye, W., Wolfe, M. S., and Selkoe, D. J. (2002) Complex N-linked glycosylated nicastrin associates with active γ-secretase and undergoes tight cellular regulation, J. Biol. Chem. 277, 35113-7.
41. Yang, D. S., Tandon, A., Chen, F., Yu, G., Yu, H., Arawaka, S., Hasegawa, H., Duthie, M., Schmidt, S. D., Ramabhadran, T. V., Nixon, R. A., Mathews, P. M., Gandy, S. E., Mount, H. T., St. George-Hyslop, P. H., and Fraser, P. E. (2002) Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins, J. Biol. Chem. 277, 28135-42.
42. Leem, J. Y., Vijayan, S., Han, P., Cai, D., Machura, M., Lopes, K. O., Veselits, M. L., Xu, H., and Thinakaran, G. (2002) Presenilin 1 is required for maturation and cell surface accumulation of nicastrin, J. Biol. Chem. 277, 19236-40.
43. Kim, T. W., Pettingel, W., Jung, Y. K., Kovacs, D. M., and Tanzi, R. E. (1997) Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease, Science 277, 373-6.
44. Hartmann, H., Busciglio, J., Baumann, K.-H., Staufenbiel. M., and Yankner, B. A. (1997) Developmental Regulation of Presenilin-1 Processing in the Brain Suggests a Role in Neuronal Differentiation, J. Biol. Chem. 272, 14505-8.
45. Nitsch, R. M., Blusztajn, J., Pittas, A. G., Slack, B. E., Growdon, J. H., and Wurtman, R. J. (1992) Evidence for a membrane defect in Alzheimer disease brain, Proc. Natl. Acad. Sci. U.S.A. 89, 1671-5.
46. Holmes-McNary, M. Q., Loy, R., Mar, M. H., Albright, C. D., and Zeisel, S. H. (1997) Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells, Brain Res. Dev. Brain Res. 101, 9-16.
47. Suomensaari, S. M., Caccavello, R., Jacobson-Croak, K., Bales, C., Doan, M., Basi, G. S., Walker, D., Anderson, J. P., and Sinha, S. (2000) Soc. Neurosci. Abstr. 26, 1283.
48. Asami-Odaka, A., Ishibashi, Y., Kikuchi, T., Kitada, C., and Suzuki, N. (1995) Long amyloid β-protein secreted from wildtype human neuroblastoma IMR-32 cells, Biochemistry 34, 10272-8.
49. Wahrle, S., Das, P., Nyborg, A. C., McLendon, C., Shoji, M., Kawarabayashi, T., Younkin, L. H., Younkin, S. G., and Golde, T. E. (2002) Cholesterol-dependent γ-secretase activity in buoyant cholesterol-rich membrane microdomains, Neurobiol Dis. 9, 11-23.
50. Burns, M., Gaynor, K., Olm, V., Mercken, M., LaFrancois, J., Wang, L., Mathews, P. M., Noble, W., Matsuoka, Y., and Duff, K. (2003) Presenilin redistribution associated with aberrant cholesterol transport enhances β-amyloid production in vivo, J. Neurosci. 23, 5645-9.
51. Runz, H., Rietdorf, J., Tomic, I., de Bernard, M., Beyreuther, K., Pepperkok, R., and Hartmann, T. (2002) Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells, J. Neurosci. 22, 1679-89.
52. Fassbender, K., Simons, M., Bergmann, C., Stroick, M., Lutjohann, D., Keller, P., Runz, H., Kuhl, S., Bertsch, T., von Bergmann, K., Hennerici, M., Beyreuther, K., and Hartmann, T. (2001) Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo, Proc. Natl. Acad. Sci. U.S.A. 98, 5856-61.
53. Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., and Simons, K. (1998) Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons, Proc. Natl. Acad. Sci. U.S.A. 95, 6460-4.
54. Fraering, P., Imhof, I., Meyer, U., Strub, J. M., van Dorsselaer, A., Vionnet, C., and Conzelmann, A. (2001) The GPI transamidase complex of Saccharomyces cerevisiae contains Gaa1p, Gpi8p, and Gpi16p, Mol. Biol. Cell. 12, 3295-306.
55. Tian, G., Sobotka-Briner, C., Zysk, J., Liu, X., Birr, C., Sylvester, M. A., Edwards, P. D., Scott, C. D., and Greenberg, B. D. (2002) Linear noncompetitive inhibition of solubilized human γ-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines, J. Biol. Chem. 277, 31499-505.
56. Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., de Saint Andrieu, P., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E., Holsztynska, E. J., Hu, K. L., Johnson-Wood, K. L., Kennedy, S. L., Kholodenko, D., Knops, J. E., Latimer, L. H., Lee, M., Liao, Z., Lieberburg, I. M., Motter, R. N., Mutter, L. C., Nietz, J., Quinn, K. P., Sacchi, K. L., Seubert, P. A., Shopp, G. M., Thorsett, E. D., Tung, J., Wu, J., Yang, S., Yin, C. T., Schenk, D. B., May, P. C., Altstiel, L. D., Bender, M. H., Boggs, L. N., Britton, T. C., Clemens, J. C., Czilli, D. L., Dieckman-McGinty, D. K., Droste, J. J., Fuson, K., Gitter, B. D., Hyslop, P. A., Johnstone, E. M., Li, W. Y., Little, S. P., Mabry, T. E., Miller, F. D., and Audia, J. E. (2001) Functional γ-secretase inhibitors reduce β-amyloid peptide levels in brain, J. Neurochem. 76, 173-81.
57. Klafki, H., Abramowski, D., Swoboda, R., Paganetti, P. A., and Staufenbiel, M. (1996) The carboxyl termini of β-amyloid peptides 1-40 and 1-42 are generated by distinct γ-secretase activities, J. Biol. Chem. 271, 28655-9.
58. Wolfe, M. S., Xia, W., Moore, C. L., Leatherwood, D. D., Ostaszewski, B., Rahmati, T., Donkor, I. O., and Selkoe, D. J. (1999) Peptidomimetic probes and molecular modeling suggest that Alzheimer's γ-secretase is an intramembrane-cleaving aspartyl protease, Biochemistry 38, 4720-7.
59. Weggen, S., Eriksen, J., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter. T., Kang, D., Marquez-Sterling, N., Golde, T. E., and Koo, E. H. (2001) A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity, Nature 414, 212-6.
60. Takahashi, Y., Hayashi, I., Tominari, Y., Rikimaru, K., Morohashi, Y., Kan, T., Natsugari, H., Fukuyama, T., Tomita, T., and Iwatsubo, T. (2003) Sulindac sulfide is a noncompetitive γ-secretase inhibitor that preferentially reduces Abeta 42 generation, J. Biol. Chem. 278, 18664-70.
61. Richardson, D. R., and Ponka, P. (1997) The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells, Biochim. Biophys. Acta 1331, 1-40.
62. Xia, W., Zhang, J., Perez, R., Koo, E. H., and Selkoe, D. J. (1997) Interaction between amyloid precursor protein and presenilins in mammalian cells: implications for the pathogenesis of Alzheimer disease, Proc. Natl. Acad. Sci. U.S.A. 94, 8208-13.
63. Murphy, M. P., Uljon, S., Golde, T. E., and Wang, R. (2002) FAD-linked mutations in presenilin 1 alter the length of Abeta peptides derived from betaAPP transmembrane domain mutants, Biochim. Biophys. Acta 1586, 199-209.
64. Lichtenthaler, S. F., Beher, D., Grimm, H. S., Wang, R., Shearman, M. S., Masters, C. L., and Beyreuther, K. (2002) The intramembrane cleavage site of the amyloid precursor protein depends on the length of its transmembrane domain, Proc. Natl. Acad. Sci. U.S.A. 99, 1365-70.
65. 1H NMR, Biochemistry 29, 5265-9.
66. Rizo, J., Blanco, F., Kobe, B., Bruch, M. D., and Gierasch, L. M. (1993) Conformational behavior of Escherichia coli OmpA signal peptides in membrane mimetic environments, Biochemistry 32, 4881-94.
67. Watanabe, Y. (2002) Effect of various mild surfactants on the reassembly of an oligomeric integral membrane protein OmpF porin, J. Protein Chem. 21, 169-75.
68. Kim, J. M., Booth, P., Allen, S. J., and Khorana, H. G. (2001) Structure and function in bacteriorhodopsin: the role of the interhelical loops in the folding and stability of bacteriorhodopsin, J. Mol. Biol. 308, 409-22.
69. Otzen, D. (2003) Folding of DsbB in mixed micelles: a kinetic analysis of the stability of a bacterial membrane protein, J. Mol. Biol. 330, 641-9.
70. Takasugi, N., Takahashi, Y., Morohashi, Y., Tomita, T., Iwatsubo, T. (2002) The mechanism of γ-secretase activities through high molecular weight complex formation of presenilins is conserved in Drosophila melanogaster and mammals, J. Biol. Chem. 277, 50198-205.