Toward Structural Elucidation of the γ-Secretase Complex

Structure

Volumn 17, Issue 3, 2009, Pages 326-334

  Li, Huilin ^a,b   Wolfe, Michael S ^c   Selkoe, Dennis J ^c  

^a BROOKHAVEN NATIONAL LABORATORY   (United States)

^b STONY BROOK UNIVERSITY   (United States)

^c Brigham and Women's Hospital Center for Neurologic Diseases   (United States)

Author keywords

CELLBIO; PROTEINS

Indexed keywords

AMYLOID BETA PROTEIN; ANTERIOR PHARYNX DEFECTIVE 1 PROTEIN; GAMMA SECRETASE; NICASTRIN; NOTCH RECEPTOR; PRESENILIN; PRESENILIN 2; PROTEASOME; PROTEIN PEN 2; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; BIOLOGICAL ACTIVITY; CRYOELECTRON MICROSCOPY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; HUMAN; MEMBRANE; NEOPLASM; NEUROFIBRILLARY TANGLE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; STOICHIOMETRY;

ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; CRYOELECTRON MICROSCOPY; HUMANS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; PRESENILINS; PROTEIN SUBUNITS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 61449208917     PISSN: 09692126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.str.2009.01.007     Document Type: Review

References (103)

1. Agirrezabala X., Lei J., Brunelle J.L., Ortiz-Meoz R.F., Green R., and Frank J. Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome. Mol. Cell 32 (2008) 190-197
2. Amor-Mahjoub M., Suppini J.P., Gomez-Vrielyunck N., and Ladjimi M. The effect of the hexahistidine-tag in the oligomerization of HSC70 constructs. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 844 (2006) 328-334
3. Barnham K.J., McKinstry W.J., Multhaup G., Galatis D., Morton C.J., Curtain C.C., Williamson N.A., White A.R., Hinds M.G., Norton R.S., et al. Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. J. Biol. Chem. 278 (2003) 17401-17407
4. Beel A.J., and Sanders C.R. Substrate specificity of gamma-secretase and other intramembrane proteases. Cell. Mol. Life Sci. 65 (2008) 1311-1334
5. Beel A.J., Mobley C.K., Kim H.J., Tian F., Hadziselimovic A., Jap B., Prestegard J.H., and Sanders C.R. Structural studies of the transmembrane C-terminal domain of the amyloid precursor protein (APP): does APP function as a cholesterol sensor?. Biochemistry 47 (2008) 9428-9446
6. Ben-Shem A., Fass D., and Bibi E. Structural basis for intramembrane proteolysis by rhomboid serine proteases. Proc. Natl. Acad. Sci. USA 104 (2007) 462-466
7. Bihel F., Das C., Bowman M.J., and Wolfe M.S. Discovery of a subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. J. Med. Chem. 47 (2004) 3931-3933
8. Bodenstaff E.R., Hoedemaeker F.J., Kuil M.E., de Vrind H.P., and Abrahams J.P. The prospects of protein nanocrystallography. Acta Crystallogr. D Biol. Crystallogr. 58 (2002) 1901-1906
9. Brunkan A.L., Martinez M., Walker E.S., and Goate A.M. Presenilin endoproteolysis is an intramolecular cleavage. Mol. Cell. Neurosci. 29 (2005) 65-73
10. Cacquevel M., Aeschbach L., Osenkowski P., Li D., Ye W., Wolfe M.S., Li H., Selkoe D.J., and Fraering P.C. Rapid purification of active gamma-secretase, an intramembrane protease implicated in Alzheimer's disease. J. Neurochem. 104 (2008) 210-220
11. Cambie R., Downing K.H., Typke D., Glaeser R.M., and Jin J. Design of a microfabricated, two-electrode phase-contrast element suitable for electron microscopy. Ultramicroscopy 107 (2007) 329-339
12. Chandramouli P., Topf M., Menetret J.F., Eswar N., Cannone J.J., Gutell R.R., Sali A., and Akey C.W. Structure of the mammalian 80S ribosome at 8.7 A resolution. Structure 16 (2008) 535-548
13. Chavez-Gutierrez L., Tolia A., Maes E., Li T., Wong P.C., and de Strooper B. Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity. J. Biol. Chem. 283 (2008) 20096-20105
14. Chen F., Hasegawa H., Schmitt-Ulms G., Kawarai T., Bohm C., Katayama T., Gu Y., Sanjo N., Glista M., Rogaeva E., et al. TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity. Nature 440 (2006) 1208-1212
15. Crystal A.S., Morais V.A., Pierson T.C., Pijak D.S., Carlin D., Lee V.M., and Doms R.W. Membrane topology of gamma-secretase component PEN-2. J. Biol. Chem. 278 (2003) 20117-20123
16. Danev R., and Nagayama K. Transmission electron microscopy with Zernike phase plate. Ultramicroscopy 88 (2001) 243-252
17. De Strooper B., Saftig P., Craessaerts K., Vanderstichele H., Guhde G., Annaert W., Von Figura K., and Van Leuven F. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391 (1998) 387-390
18. 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., et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398 (1999) 518-522
19. Edbauer D., Winkler E., Regula J.T., Pesold B., Steiner H., and Haass C. Reconstitution of gamma-secretase activity. Nat. Cell Biol. 5 (2003) 486-488
20. Fagan R., Swindells M., Overington J., and Weir M. Nicastrin, a presenilin-interacting protein, contains an aminopeptidase/transferrin receptor superfamily domain. Trends Biochem. Sci. 26 (2001) 213-214
21. Feng L., Yan H., Wu Z., Yan N., Wang Z., Jeffrey P.D., and Shi Y. Structure of a site-2 protease family intramembrane metalloprotease. Science 318 (2007) 1608-1612
22. Fortna R.R., Crystal A.S., Morais V.A., Pijak D.S., Lee V.M., and Doms R.W. Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of the gamma-secretase complex. J. Biol. Chem. 279 (2004) 3685-3693
23. Fraering P.C., LaVoie M.J., Ye W., Ostaszewski B.L., Kimberly W.T., Selkoe D.J., and Wolfe M.S. Detergent-dependent dissociation of active gamma-secretase reveals an interaction between Pen-2 and PS1-NTF and offers a model for subunit organization within the complex. Biochemistry 43 (2004) 323-333
24. Fraering P.C., Ye W., Strub J.M., Dolios G., LaVoie M.J., Ostaszewski B.L., van Dorsselaer A., Wang R., Selkoe D.J., and Wolfe M.S. Purification and characterization of the human gamma-secretase complex. Biochemistry 43 (2004) 9774-9789
25. Fujiyoshi Y., and Unwin N. Electron crystallography of proteins in membranes. Curr. Opin. Struct. Biol. 18 (2008) 587-592
26. Glaeser R., Downing K., DeRosier D., Chiu W., and Frank J. Electron Crystallography of Biological Macromolecules (2007), Oxford University Press, New York
27. Goate A., Chartier-Harlin M.C., Mullan M., Brown J., Crawford F., Fidani L., Giuffra L., Haynes A., Irving N., James L., et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349 (1991) 704-706
28. Gonen T., Cheng Y., Sliz P., Hiroaki Y., Fujiyoshi Y., Harrison S.C., and Walz T. Lipid-protein interactions in double-layered two-dimensional AQP0 crystals. Nature 438 (2005) 633-638
29. Gorman P.M., Kim S., Guo M., Melnyk R.A., McLaurin J., Fraser P.E., Bowie J.U., and Chakrabartty A. Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants. BMC Neurosci. 9 (2008) 17
30. Gouaux E., and Mackinnon R. Principles of selective ion transport in channels and pumps. Science 310 (2005) 1461-1465
31. Ha Y. Structural principles of intramembrane proteases. Curr. Opin. Struct. Biol. 17 (2007) 405-411
32. Hardy J., and Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297 (2002) 353-356
33. Hebert S.S., Godin C., and Levesque G. Oligomerization of human presenilin-1 fragments. FEBS Lett. 550 (2003) 30-34
34. Hemming M.L., Elias J.E., Gygi S.P., and Selkoe D.J. Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. PLoS Biol. 6 (2008) e257
35. Henderson R. The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules. Q. Rev. Biophys. 28 (1995) 171-193
36. Henricson A., Kall L., and Sonnhammer E.L. A novel transmembrane topology of presenilin based on reconciling experimental and computational evidence. FEBS J. 272 (2005) 2727-2733
37. Herreman A., Van Gassen G., Bentahir M., Nyabi O., Craessaerts K., Mueller U., Annaert W., and De Strooper B. gamma-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation. J. Cell Sci. 116 (2003) 1127-1136
38. Jiang J., and Sweet R.M. Protein Data Bank depositions from synchrotron sources. J. Synchrotron Radiat. 11 (2004) 319-327
39. Jiang Q.X., Wang D.N., and MacKinnon R. Electron microscopic analysis of KvAP voltage-dependent K+ channels in an open conformation. Nature 430 (2004) 806-810
40. Jiang W., Baker M.L., Jakana J., Weigele P.R., King J., and Chiu W. Backbone structure of the infectious epsilon15 virus capsid revealed by electron cryomicroscopy. Nature 451 (2008) 1130-1134
41. Kim J., Kleizen B., Choy R., Thinakaran G., Sisodia S.S., and Schekman R.W. Biogenesis of gamma-secretase early in the secretory pathway. J. Cell Biol. 179 (2007) 951-963
42. Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S., and Selkoe D.J. Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc. Natl. Acad. Sci. USA 100 (2003) 6382-6387
43. Kopan R., and Ilagan M.X. Gamma-secretase: proteasome of the membrane?. Nat. Rev. Mol. Cell Biol. 5 (2004) 499-504
44. Kornilova A.Y., Bihel F., Das C., and Wolfe M.S. The initial substrate-binding site of gamma-secretase is located on presenilin near the active site. Proc. Natl. Acad. Sci. USA 102 (2005) 3230-3235
45. Kornilova A.Y., Kim J., Laudon H., and Wolfe M.S. Deducing the transmembrane domain organization of presenilin-1 in gamma-secretase by cysteine disulfide cross-linking. Biochemistry 45 (2006) 7598-7604
46. Lai M.T., Chen E., Crouthamel M.C., DiMuzio-Mower J., Xu M., Huang Q., Price E., Register R.B., Shi X.P., Donoviel D.B., et al. Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities. J. Biol. Chem. 278 (2003) 22475-22481
47. Laudon H., Hansson E.M., Melen K., Bergman A., Farmery M.R., Winblad B., Lendahl U., von Heijne G., and Naslund J. A nine transmembrane domain topology for presenilin 1. J. Biol. Chem. 280 (2005) 35352-35360
48. LaVoie M.J., Fraering P.C., Ostaszewski B.L., Ye W., Kimberly W.T., Wolfe M.S., and Selkoe D.J. Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin. J. Biol. Chem. 278 (2003) 37213-37222
49. Lazarov V.K., Fraering P.C., Ye W., Wolfe M.S., Selkoe D.J., and Li H. Electron microscopic structure of purified, active gamma-secretase reveals an aqueous intramembrane chamber and two pores. Proc. Natl. Acad. Sci. USA 103 (2006) 6889-6894
50. Lemieux M.J., Fischer S.J., Cherney M.M., Bateman K.S., and James M.N. The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis. Proc. Natl. Acad. Sci. USA 104 (2007) 750-754
51. Li H., Qian L., Chen Z., Thibault D., Liu G., Liu T., and Thanassi D.G. The outer membrane usher forms a twin-pore secretion complex. J. Mol. Biol. 344 (2004) 1397-1407
52. Martin L., Fluhrer R., Reiss K., Kremmer E., Saftig P., and Haass C. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. J. Biol. Chem. 283 (2008) 1644-1652
53. Matadeen R., Patwardhan A., Gowen B., Orlova E.V., Pape T., Cuff M., Mueller F., Brimacombe R., and van Heel M. The Escherichia coli large ribosomal subunit at 7.5 A resolution. Structure 7 (1999) 1575-1583
54. Moon R.T., Bowerman B., Boutros M., and Perrimon N. The promise and perils of Wnt signaling through beta-catenin. Science 296 (2002) 1644-1646
55. Munter L.M., Voigt P., Harmeier A., Kaden D., Gottschalk K.E., Weise C., Pipkorn R., Schaefer M., Langosch D., and Multhaup G. GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42. EMBO J. 26 (2007) 1702-1712
56. Narayanan S., Sato T., and Wolfe M.S. A C-terminal region of signal peptide peptidase defines a functional domain for intramembrane aspartic protease catalysis. J. Biol. Chem. 282 (2007) 20172-20179
57. Niimura M., Isoo N., Takasugi N., Tsuruoka M., Ui-Tei K., Saigo K., Morohashi Y., Tomita T., and Iwatsubo T. Aph-1 contributes to the stabilization and trafficking of the gamma-secretase complex through mechanisms involving intermolecular and intramolecular interactions. J. Biol. Chem. 280 (2005) 12967-12975
58. Ogura T., Mio K., Hayashi I., Miyashita H., Fukuda R., Kopan R., Kodama T., Hamakubo T., Iwatsubo T., Tomita T., and Sato C. Three-dimensional structure of the gamma-secretase complex. Biochem. Biophys. Res. Commun. 343 (2006) 525-534
59. Osenkowski P., Ye W., Wang R., Wolfe M.S., and Selkoe D.J. Direct and potent regulation of gamma -secretase by its lipid microenvironment. J. Biol. Chem. 283 (2008) 22529-22540
60. Osenkowski P., Li H., Ye W., Li D., Aeschbach L., Fraering P.C., Wolfe M.S., Selkoe D.J., and Li H. Cryoelectron microscopy structure of purified gamma-secretase at 12 A resolution. J. Mol. Biol. 385 (2009) 642-652
61. Ren Z., Schenk D., Basi G.S., and Shapiro I.P. Amyloid beta-protein precursor juxtamembrane domain regulates specificity of gamma-secretase-dependent cleavages. J. Biol. Chem. 282 (2007) 35350-35360
62. Sato C., Morohashi Y., Tomita T., and Iwatsubo T. Structure of the catalytic pore of gamma-secretase probed by the accessibility of substituted cysteines. J. Neurosci. 26 (2006) 12081-12088
63. Sato T., Diehl T.S., Narayanan S., Funamoto S., Ihara Y., De Strooper B., Steiner H., Haass C., and Wolfe M.S. Active gamma-secretase complexes contain only one of each component. J. Biol. Chem. 282 (2007) 33985-33993
64. Scheuner D., Eckman C., Jensen M., Song X., Citron M., Suzuki N., Bird T.D., Hardy J., Hutton M., Kukull W., et al. Secreted amyloid beta-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 (1996) 864-870
65. Schroeter E.H., Ilagan M.X., Brunkan A.L., Hecimovic S., Li Y.M., Xu M., Lewis H.D., Saxena M.T., De Strooper B., Coonrod A., et al. A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc. Natl. Acad. Sci. USA 100 (2003) 13075-13080
66. Selkoe D.J., and Wolfe M.S. Presenilin: running with scissors in the membrane. Cell 131 (2007) 215-221
67. Serban G., Kouchi Z., Baki L., Georgakopoulos A., Litterst C.M., Shioi J., and Robakis N.K. Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability. J. Biol. Chem. 280 (2005) 36007-36012
68. Serneels L., Dejaegere T., Craessaerts K., Horre K., Jorissen E., Tousseyn T., Hebert S., Coolen M., Martens G., Zwijsen A., et al. Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo. Proc. Natl. Acad. Sci. USA 102 (2005) 1719-1724
69. Shah S., Lee S., Tabuchi K., Hao Y., Yu C., LaPlant Q., Ball H., Dann III C.E., Südhof T., and Yu G. Nicastrin functions as a gamma-secretase-substrate receptor. Cell 122 (2005) 435-447
70. Shankar G.M., Li S., Mehta T.H., Garcia-Munoz A., Shepardson N.E., Smith I., Brett F.M., Farrell M.A., Rowan M.J., Lemere C.A., et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 14 (2008) 837-842
71. Shih Ie.M., and Wang T.L. Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res. 67 (2007) 1879-1882
72. Shirotani K., Edbauer D., Capell A., Schmitz J., Steiner H., and Haass C. Gamma-secretase activity is associated with a conformational change of nicastrin. J. Biol. Chem. 278 (2003) 16474-16477
73. Shirotani K., Edbauer D., Kostka M., Steiner H., and Haass C. Immature nicastrin stabilizes APH-1 independent of PEN-2 and presenilin: identification of nicastrin mutants that selectively interact with APH-1. J. Neurochem. 89 (2004) 1520-1527
74. Shirotani K., Tomioka M., Kremmer E., Haass C., and Steiner H. Pathological activity of familial Alzheimer's disease-associated mutant presenilin can be executed by six different gamma-secretase complexes. Neurobiol. Dis. 27 (2007) 102-107
75. Small D.H. Is gamma-secretase a multienzyme complex for membrane protein degradation? Models and speculations. Peptides 23 (2002) 1317-1321
76. Smith I.F., Green K.N., and LaFerla F.M. Calcium dysregulation in Alzheimer's disease: recent advances gained from genetically modified animals. Cell Calcium 38 (2005) 427-437
77. Spasic D., and Annaert W. Building gamma-secretase: the bits and pieces. J. Cell Sci. 121 (2008) 413-420
78. Spasic D., Tolia A., Dillen K., Baert V., De Strooper B., Vrijens S., and Annaert W. Presenilin-1 maintains a nine-transmembrane topology throughout the secretory pathway. J. Biol. Chem. 281 (2006) 26569-26577
79. St. George-Hyslop P.H. Piecing together Alzheimer's. Sci. Am. 283 (2000) 76-83
80. Steiner H., Winkler E., and Haass C. Chemical crosslinking provides a model of the gamma-secretase complex subunit architecture and evidence for close proximity of the C-terminal fragment of presenilin with APH-1. J. Biol. Chem. 283 (2008) 34677-34686
81. Struhl G., and Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398 (1999) 522-525
82. Takasugi N., Tomita T., Hayashi I., Tsuruoka M., Niimura M., Takahashi Y., Thinakaran G., and Iwatsubo T. The role of presenilin cofactors in the gamma-secretase complex. Nature 422 (2003) 438-441
83. Tanzi R.E., McClatchey A.I., Lamperti E.D., Villa-Komaroff L., Gusella J.F., and Neve R.L. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature 331 (1988) 528-530
84. Tate C.G. Overexpression of mammalian integral membrane proteins for structural studies. FEBS Lett. 504 (2001) 94-98
85. Thinakaran G., Regard J.B., Bouton C.M., Harris C.L., Price D.L., Borchelt D.R., and Sisodia S.S. Stable association of presenilin derivatives and absence of presenilin interactions with APP. Neurobiol. Dis. 4 (1998) 438-453
86. Thinakaran G., Teplow D.B., Siman R., Greenberg B., and Sisodia S.S. Metabolism of the "Swedish" amyloid precursor protein variant in neuro2a (N2a) cells. Evidence that cleavage at the "beta-secretase" site occurs in the golgi apparatus. J. Biol. Chem. 271 (1996) 9390-9397
87. Tolia A., Chavez-Gutierrez L., and De Strooper B. Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complex. J. Biol. Chem. 281 (2006) 27633-27642
88. Tolia A., Horre K., and De Strooper B. Transmembrane domain 9 of presenilin determines the dynamic conformation of the catalytic site of gamma-secretase. J. Biol. Chem. 283 (2008) 19793-19803
89. Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., Serneels L., De Strooper B., Yu G., and Bezprozvanny I. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. Cell 126 (2006) 981-993
90. Urban S., and Shi Y. Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases. Curr. Opin. Struct. Biol. 8 (2008) 432-441
91. Wakabayashi T., and De Strooper B. Presenilins: members of the gamma-secretase quartets, but part-time soloists too. Physiology (Bethesda) 23 (2008) 194-204
92. Wang Y., and Ha Y. The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain. Mol. Cell 15 (2004) 343-353
93. Wang Y., Zhang Y., and Ha Y. Crystal structure of a rhomboid family intramembrane protease. Nature 444 (2006) 179-180
94. Wolfe M.S. Inhibition and modulation of gamma-secretase for Alzheimer's disease. Neurotherapeutics 5 (2008) 391-398
95. Wolfe M.S., and Guenette S.Y. APP at a glance. J. Cell Sci. 120 (2007) 3157-3161
96. Wolfe M.S., and Kopan R. Intramembrane proteolysis: theme and variations. Science 305 (2004) 1119-1123
97. Wolfe M.S., Xia W., Ostaszewski B.L., Diehl T.S., Kimberly W.T., and Selkoe D.J. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398 (1999) 513-517
98. Wu J., and Filutowicz M. Hexahistidine (His6)-tag dependent protein dimerization: a cautionary tale. Acta Biochim. Pol. 46 (1999) 591-599
99. Wu Z., Yan N., Feng L., Oberstein A., Yan H., Baker R.P., Gu L., Jeffrey P.D., Urban S., and Shi Y. Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nat. Struct. Mol. Biol. 13 (2006) 1084-1091
100. Yu X., Jin L., and Zhou Z.H. 3.88 A structure of cytoplasmic polyhedrosis virus by cryo-electron microscopy. Nature 453 (2008) 415-419
101. Zhang X., Settembre E., Xu C., Dormitzer P.R., Bellamy R., Harrison S.C., and Grigorieff N. Near-atomic resolution using electron cryomicroscopy and single-particle reconstruction. Proc. Natl. Acad. Sci. USA 105 (2008) 1867-1872
102. Zhang Z., Hartmann H., Do V.M., Abramowski D., Sturchler-Pierrat C., Staufenbiel M., Sommer B., van de Wetering M., Clevers H., Saftig P., et al. Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 395 (1998) 698-702
103. Zhou S., Zhou H., Walian P.J., and Jap B.K. CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production. Proc. Natl. Acad. Sci. USA 102 (2005) 7499-7504