Nicastrin functions to sterically hinder γ-secretase-substrate interactions driven by substrate transmembrane domain

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 5, 2016, Pages E509-E518

  Bolduc, David M ^a   Montagna, Daniel R ^a   Gu, Yongli ^a   Selkoe, Dennis J ^a   Wolfe, Michael S ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Azheimer's disease; Intramembrane cleaving protease; Nicastrin; Notch; secretase

Indexed keywords

GAMMA SECRETASE; NICASTRIN; LIPID BILAYER; MEMBRANE PROTEIN; NICASTRIN PROTEIN; SECRETASE;

ARTICLE; CATALYSIS; ENZYME SUBSTRATE; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN INTERACTION; STEREOSPECIFICITY; ENZYME SPECIFICITY; LIPID BILAYER; METABOLISM; PHYSIOLOGY;

AMYLOID PRECURSOR PROTEIN SECRETASES; LIPID BILAYERS; MEMBRANE GLYCOPROTEINS; SUBSTRATE SPECIFICITY;

EID: 84956700602     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1512952113     Document Type: Article

References (67)

1. Urban S (2013) Mechanisms and cellular functions of intramembrane proteases. Biochim Biophys Acta 1828 (12): 2797-2800.
2. Huppert SS, et al. (2000) Embryonic lethality in mice homozygous for a processingdeficient allele of Notch1. Nature 405 (6789): 966-970.
3. Rawson RB, et al. (1997) Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Mol Cell 1 (1): 47-57.
4. Ye J, et al. (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell 6 (6): 1355-1364.
5. Stevenson LG, et al. (2007) Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase. Proc Natl Acad Sci USA 104 (3): 1003-1008.
6. Moin SM, Urban S (2012) Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics. eLife 1: E00173.
7. Dickey SW, Baker RP, Cho S, Urban S (2013) Proteolysis inside the membrane is a rategoverned reaction not driven by substrate affinity. Cell 155 (6): 1270-1281.
8. Freeman M (2004) Proteolysis within the membrane: Rhomboids revealed. Nat Rev Mol Cell Biol 5 (3): 188-197.
9. Rawson RB (2013) The site-2 protease. Biochim Biophys Acta 1828 (12): 2801-2807.
10. Voss M, Schröder B, Fluhrer R (2013) Mechanism, specificity, and physiology of signal peptide peptidase (SPP) and SPP-like proteases. Biochim Biophys Acta 1828 (12): 2828-2839.
11. Struhl G, Adachi A (2000) Requirements for presenilin-dependent cleavage of notch and other transmembrane proteins. Mol Cell 6 (3): 625-636.
12. Haapasalo A, Kovacs DM (2011) The many substrates of presenilin/?-secretase. J Alzheimers Dis 25 (1): 3-28.
13. Struhl G, Greenwald I (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398 (6727): 522-525.
14. De Strooper B, et al. (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398 (6727): 518-522.
15. Mumm JS, et al. (2000) A ligand-induced extracellular cleavage regulates gammasecretase-like proteolytic activation of Notch1. Mol Cell 5 (2): 197-206.
16. Kopan R, Ilagan MXG (2009) The canonical Notch signaling pathway: Unfolding the activation mechanism. Cell 137 (2): 216-233.
17. Wolfe MS, et al. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398 (6727): 513-517.
18. Beel AJ, Sanders CR (2008) Substrate specificity of gamma-secretase and other intramembrane proteases. Cell Mol Life Sci 65 (9): 1311-1334.
19. Kopan R, Ilagan MXG (2004) Gamma-secretase: Proteasome of the membrane? Nat Rev Mol Cell Biol 5 (6): 499-504.
20. Francis R, et al. (2002) aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3 (1): 85-97.
21. Edbauer D, et al. (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5 (5): 486-488.
22. Kimberly WT, et al. (2003) Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci USA 100 (11): 6382-6387.
23. Takasugi N, et al. (2003) The role of presenilin cofactors in the gamma-secretase complex. Nature 422 (6930): 438-441.
24. Lu P, et al. (2014) Three-dimensional structure of human ?-secretase. Nature 512 (7513): 166-170.
25. Li YM, et al. (2000) Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405 (6787): 689-694.
26. Esler WP, et al. (2000) Transition-state analogue inhibitors of gamma-secretase bind directly to presenilin-1. Nat Cell Biol 2 (7): 428-434.
27. Thinakaran G, et al. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17 (1): 181-190.
28. Fukumori A, Fluhrer R, Steiner H, Haass C (2010) Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretasemediated intramembrane proteolysis. J Neurosci 30 (23): 7853-7862.
29. Ahn K, et al. (2010) Activation and intrinsic gamma-secretase activity of presenilin 1. Proc Natl Acad Sci USA 107 (50): 21435-21440.
30. LaVoie MJ, et al. (2003) Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin. J Biol Chem 278 (39): 37213-37222.
31. Gu Y, et al. (2003) APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes. J Biol Chem 278 (9): 7374-7380.
32. Yu G, et al. (2000) Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407 (6800): 48-54.
33. Kimberly WT, et al. (2002) Complex N-linked glycosylated nicastrin associates with active gamma-secretase and undergoes tight cellular regulation. J Biol Chem 277 (38): 35113-35117.
34. Xie T, et al. (2014) Crystal structure of the ?-secretase component nicastrin. Proc Natl Acad Sci USA 111 (37): 13349-13354.
35. Shah S, et al. (2005) Nicastrin functions as a gamma-secretase-substrate receptor. Cell 122 (3): 435-447.
36. Dries DR, et al. (2009) Glu-333 of nicastrin directly participates in gamma-secretase activity. J Biol Chem 284 (43): 29714-29724.
37. Chávez-Gutiérrez L, et al. (2008) Glu (332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activity. J Biol Chem 283 (29): 20096-20105.
38. Zhao G, Liu Z, Ilagan MXG, Kopan R (2010) Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. J Neurosci 30 (5): 1648-1656.
39. Bai X-C, et al. (2015) An atomic structure of human ?-secretase. Nature 525 (7568): 212-217.
40. Sun L, et al. (2015) Structural basis of human ?-secretase assembly. Proc Natl Acad Sci USA 112 (19): 6003-6008.
41. Fraering PC, et al. (2004) Purification and characterization of the human gammasecretase complex. Biochemistry 43 (30): 9774-9789.
42. Dawson PE, Muir TW, Clark-Lewis I, Kent SB (1994) Synthesis of proteins by native chemical ligation. Science 266 (5186): 776-779.
43. Tian Y, Bassit B, Chau D, Li Y-M (2010) An APP inhibitory domain containing the Flemish mutation residue modulates gamma-secretase activity for Abeta production. Nat Struct Mol Biol 17 (2): 151-158.
44. Funamoto S, et al. (2013) Substrate ectodomain is critical for substrate preference and inhibition of ?-secretase. Nat Commun 4: 2529.
45. Quintero-Monzon O, et al. (2011) Dissociation between the processivity and total activity of ?-secretase: Implications for the mechanism of Alzheimer's disease-causing presenilin mutations. Biochemistry 50 (42): 9023-9035.
46. Muir TW, Sondhi D, Cole PA (1998) Expressed protein ligation: A general method for protein engineering. Proc Natl Acad Sci USA 95 (12): 6705-6710.
47. Li X, et al. (2013) Structure of a presenilin family intramembrane aspartate protease. Nature 493 (7430): 56-61.
48. Dang S, et al. (2015) Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH. Proc Natl Acad Sci USA 112 (11): 3344-3349.
49. Lazarov VK, et al. (2006) Electron microscopic structure of purified, active gammasecretase reveals an aqueous intramembrane chamber and two pores. Proc Natl Acad Sci USA 103 (18): 6889-6894.
50. Osenkowski P, et al. (2009) Cryoelectron microscopy structure of purified gammasecretase at 12 A resolution. J Mol Biol 385 (2): 642-652.
51. Li Y, et al. (2014) Structural interactions between inhibitor and substrate docking sites give insight into mechanisms of human PS1 complexes. Structure 22 (1): 125-135.
52. Pamrén A, et al. (2011) Mutations in nicastrin protein differentially affect amyloid beta-peptide production and Notch protein processing. J Biol Chem 286 (36): 31153-31158.
53. Fluhrer R, et al. (2011) The Nicastrin ectodomain adopts a highly thermostable structure. Biol Chem 392 (11): 995-1001.
54. Bolduc D, et al. (2013) Phosphorylation-mediated PTEN conformational closure and deactivation revealed with protein semisynthesis. eLife 2: E00691.
55. Wolfe MS, Selkoe DJ (2014) ?-secretase: A horseshoe structure brings good luck. Cell 158 (2): 247-249.
56. Fernandez MA, Klutkowski JA, Freret T, Wolfe MS (2014) Alzheimer presenilin-1 mutations dramatically reduce trimming of long amyloid β-peptides (Aβ) by ?-secretase to increase 42-to-40-residue Aβ. J Biol Chem 289 (45): 31043-31052.
57. Chavez-Guti?rrez L, et al. (2012) The mechanism of ?-secretase dysfunction in familial Alzheimer disease. EMBO J 31 (10): 2261-2274.
58. McConnachie G, Pass I, Walker SM, Downes CP (2003) Interfacial kinetic analysis of the tumour suppressor phosphatase, PTEN: Evidence for activation by anionic phospholipids. Biochem J 371 (Pt 3): 947-955.
59. Urban S, Lee JR, Freeman M (2002) A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands. EMBO J 21 (16): 4277-4286.
60. Deas E, et al. (2011) PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 20 (5): 867-879.
61. Friedman JI, Stivers JT (2010) Detection of damaged DNA bases by DNA glycosylase enzymes. Biochemistry 49 (24): 4957-4967.
62. Kroos L, Akiyama Y (2013) Biochemical and structural insights into intramembrane metalloprotease mechanisms. Biochim Biophys Acta 1828 (12): 2873-2885.
63. Hizukuri Y, et al. (2014) A structure-based model of substrate discrimination by a noncanonical PDZ tandem in the intramembrane-cleaving protease RseP. Structure 22 (2): 326-336.
64. Eggert S, et al. (2004) The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilonlike cleavages: Modulation of APLP-1 processing by n-glycosylation. J Biol Chem 279 (18): 18146-18156.
65. Luo X, et al. (2011) Cleavage of neuregulin-1 by BACE1 or ADAM10 protein produces differential effects on myelination. J Biol Chem 286 (27): 23967-23974.
66. Zhang YW, et al. (2005) Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. J Biol Chem 280 (17): 17020-17026.
67. Kamp F, et al. (2015) Intramembrane proteolysis of β-amyloid precursor protein by ?-secretase is an unusually slow process. Biophys J 108 (5): 1229-1237.