Insights into membrane-bound presenilin 2 from all-atom molecular dynamics simulations

References

• Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindah, E. (2015). Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1–2, 19–25. doi:10.1016/j.softx.2015.06.001
   Google Scholar
• Adcock, S. A., & McCammon, J. A. (2006). Molecular dynamics: Survey of methods for simulating the activity of proteins. Chemical Reviews, 106(5), 1589–1615. doi:10.1021/cr040426m
   PubMed Web of Science ®Google Scholar
• Aguayo-Ortiz, R., Chávez-García, C., Straub, J. E., & Dominguez, L. (2017). Characterizing the structural ensemble of γ-secretase using a multiscale molecular dynamics approach. Chemical Science, 8(8), 5576–5584. doi:10.1039/c7sc00980a
   PubMed Web of Science ®Google Scholar
• Aguayo-Ortiz, R., Straub, J. E., & Dominguez, L. (2018). Influence of membrane lipid composition on the structure and activity of γ-secretase. Physical Chemistry Chemical Physics, 20(43), 27294–27304. doi:10.1039/c8cp04138e
   PubMed Web of Science ®Google Scholar
• Bai, X., Rajendra, E., Yang, G., Shi, Y., & Scheres, S. H. (2015). Sampling the conformational space of the catalytic subunit of human γ-secretase. eLife, 4, 551–560. doi:10.7554/eLife.11182
   Web of Science ®Google Scholar
• Bai, X-C., Yan, C., Yang, G., Lu, P., Ma, D., Sun, L., … Shi, Y. (2015). An atomic structure of human γ-secretase. Nature, 525(7568), 212–218. doi:10.1038/nature14892
   PubMed Web of Science ®Google Scholar
• Ballard, C., Gauthier, S., Corbett, A., Brayne, C., Aarsland, D., & Jones, E. (2011). Alzheimer’s disease. The Lancet, 377(9770), 1019–1031. doi:10.1016/S0140-6736(10)61349-9
   PubMed Web of Science ®Google Scholar
• Begley, J. G., Duan, W., Chan, S., Duff, K., & Mattson, M. P. (2008). Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin‐1 mutant mice. Journal of Neurochemistry, 72(3), 1030–1039. doi:10.1046/j.1471-4159.1999.0721030.x
   Google Scholar
• Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., & Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. The Journal of Chemical Physics, 81(8), 3684–3690. doi:10.1063/1.448118
   Web of Science ®Google Scholar
• Bolduc, D. M., Montagna, D. R., Gu, Y., Selkoe, D. J., & Wolfe, M. S. (2016). Nicastrin functions to sterically hinder γ-secretase–substrate interactions driven by substrate transmembrane domain. Proceedings of the National Academy of Sciences, 113(5), E509–E518. doi:10.1073/pnas.1512952113
   PubMed Web of Science ®Google Scholar
• Bolduc, D. M., Montagna, D. R., Seghers, M. C., Wolfe, M. S., & Selkoe, D. J. (2016). The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase. eLife, 5, e17578. doi:10.7554/eLife.17578
   PubMed Web of Science ®Google Scholar
• Brunello, L., Zampese, E., Florean, C., Pozzan, T., Pizzo, P., & Fasolato, C. (2009). Presenilin‐2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake. Journal of Cellular and Molecular Medicine, 13(9b), 3358–3369. doi:10.1111/j.1582-4934.2009.00755.x
   PubMed Web of Science ®Google Scholar
• Capriotti, E., Fariselli, P., & Casadio, R. (2005). I-Mutant2.0: Predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Research, 33(Web Server), W306–W310. doi:10.1093/nar/gki375
   PubMed Web of Science ®Google Scholar
• Capriotti, E., Fariselli, P., Rossi, I., & Casadio, R. (2008). A three-state prediction of single point mutations on protein stability changes. BMC Bioinformatics, 9(Suppl 2), S6. doi:10.1186/1471-2105-9-S2-S6
   PubMed Web of Science ®Google Scholar
• Chávez-Gutiérrez, L., Bammens, L., Benilova, I., Vandersteen, A., Benurwar, M., Borgers, M., … De Strooper, B. (2012). The mechanism of γ-secretase dysfunction in familial Alzheimer disease. The EMBO Journal, 31(10), 2261–2274. doi:10.1038/emboj.2012.79
   PubMed Web of Science ®Google Scholar
• Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., … Richardson, D. C. (2010). MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D Biological Crystallography, 66(1), 12–21. doi:10.1107/S0907444909042073
   PubMed Web of Science ®Google Scholar
• Colovos, C., & Yeates, T. O. (1993). Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Science, 2(9), 1511–1519. doi:10.1002/pro.5560020916
   PubMed Web of Science ®Google Scholar
• Contino, S., Porporato, P. E., Bird, M., Marinangeli, C., Opsomer, R., Sonveaux, P., … Kienlen-Campard, P. (2017). Presenilin 2-dependent maintenance of mitochondrial oxidative capacity and morphology. Frontiers in Physiology, 8, 796. doi:10.3389/fphys.2017.00796
   PubMed Web of Science ®Google Scholar
• Das, H. K., Tchedre, K., & Mueller, B. (2012). Repression of transcription of presenilin-1 inhibits gamma-secretase independent ER Ca(2)(+) leak that is impaired by FAD mutations. Journal of Neurochemistry, 122(3), 487–500. doi:10.1111/j.1471-4159.2012.07794.x
   PubMed Web of Science ®Google Scholar
• Daura, X., Gademann, K., Jaun, B., Seebach, D., Van Gunsteren, W. F., & Mark, A. E. (1999). Peptide folding: When simulation meets experiment. Angewandte Chemie International Edition, 38(1-2), 236–240. doi:10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M
   PubMed Web of Science ®Google Scholar
• De Strooper, B. (2007). Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Reports, 8(2), 141–146. doi:10.1038/sj.embor.7400897
   PubMed Web of Science ®Google Scholar
• De Strooper, B., Iwatsubo, T., & Wolfe, M. S. (2012). Presenilins and γ-secretase: Structure, function, and role in Alzheimer disease. Cold Spring Harbor Perspectives in Medicine, 2(1), a006304. doi:10.1101/cshperspect.a006304
   PubMed Web of Science ®Google Scholar
• De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., … Van Leuven, F. (1998). Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature, 391(6665), 387–390. doi:10.1038/34910
   PubMed Web of Science ®Google Scholar
• Duggan, S. P., & McCarthy, J. V. (2016). Beyond γ-secretase activity: The multifunctional nature of presenilins in cell signalling pathways. Cellular Signalling, 28(1), 1–11. doi:10.1016/j.cellsig.2015.10.006
   PubMed Web of Science ®Google Scholar
• Feng, L., Yan, H., Wu, Z., Yan, N., Wang, Z., Jeffrey, P. D., & Shi, Y. (2007). Structure of a site-2 protease family intramembrane metalloprotease. Science, 318(5856), 1608–1612. doi:10.1126/science.1150755
   PubMed Web of Science ®Google Scholar
• Filadi, R., Greotti, E., Turacchio, G., Luini, A., Pozzan, T., & Pizzo, P. (2016). Presenilin 2 modulates endoplasmic reticulum-mitochondria coupling by tuning the antagonistic effect of mitofusin 2. Cell Reports, 15(10), 2226–2238. doi:10.1016/J.CELREP.2016.05.013
   PubMed Web of Science ®Google Scholar
• Finckh, U., Müller-Thomsen, T., Mann, U., Eggers, C., Marksteiner, J., Meins, W., … Gal, A. (2000). High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. The American Journal of Human Genetics, 66(1), 110–117. doi:10.1086/302702
   PubMed Web of Science ®Google Scholar
• Greotti, E., Capitanio, P., Wong, A., Pozzan, T., Pizzo, P., & Pendin, D. (2019). Familial Alzheimer’s disease-linked presenilin mutants and intracellular Ca2+ handling: A single-organelle, FRET-based analysis. Cell Calcium, 79, 44–56. doi:10.1016/j.ceca.2019.02.005
   PubMed Web of Science ®Google Scholar
• Guo, Q., Furukawa, K., Sopher, B. L., Pham, D. G., Xie, J., Robinson, N., … Mattson, M. P. (1996). Alzheimer’s PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid beta-peptide. NeuroReport, 8(1), 379–383. doi:10.1097/00001756-199612200-00074
   PubMed Web of Science ®Google Scholar
• Ha, Y., Akiyama, Y., & Xue, Y. (2013). Structure and mechanism of rhomboid protease. Journal of Biological Chemistry, 288(22), 15430. doi:10.1074/jbc.R112.422378
   PubMed Web of Science ®Google Scholar
• Hekkelman, M. L., Te Beek, T. A. H., Pettifer, S. R., Thorne, D., Attwood, T. K., & Vriend, G. (2010). WIWS: A protein structure bioinformatics web service collection. Nucleic Acids Research, 38(Web Server), W719–723. doi:10.1093/nar/gkq453
   PubMedGoogle Scholar
• Heo, L., Park, H., & Seok, C. (2013). GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic Acids Research, 41(W1), W384–W388. doi:10.1093/nar/gkt458
   PubMed Web of Science ®Google Scholar
• Hizukuri, Y., Oda, T., Tabata, S., Tamura-Kawakami, K., Oi, R., Sato, M., … Nogi, T. (2014). A structure-based model of substrate discrimination by a noncanonical PDZ tandem in the intramembrane-cleaving protease RseP. Structure, 22(2), 326–336. doi:10.1016/j.str.2013.12.003
   PubMed Web of Science ®Google Scholar
• Holmes, O., Paturi, S., Selkoe, D. J., & Wolfe, M. S. (2014). Pen-2 is essential for γ-secretase complex stability and trafficking but partially dispensable for endoproteolysis. Biochemistry, 53(27), 4393–4406. doi:10.1021/bi500489j
   PubMed Web of Science ®Google Scholar
• Holmes, O., Paturi, S., Ye, W., Wolfe, M. S., & Selkoe, D. J. (2012). Effects of membrane lipids on the activity and processivity of purified γ-secretase. Biochemistry, 51(17), 3565–3575. doi:10.1021/bi300303g
   PubMed Web of Science ®Google Scholar
• Honarnejad, K., & Herms, J. (2012). Presenilins: Role in calcium homeostasis. The International Journal of Biochemistry & Cell Biology, 44(11), 1983–1986. doi:10.1016/j.biocel.2012.07.019
   PubMed Web of Science ®Google Scholar
• Huang, J., Rauscher, S., Nawrocki, G., Ran, T., Feig, M., de Groot, B. L., … MacKerell, A. D. (2017). CHARMM36m: An improved force field for folded and intrinsically disordered proteins. Nature Methods, 14(1), 71–73. doi:10.1038/nmeth.4067
   PubMed Web of Science ®Google Scholar
• Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. doi:10.1016/0263-7855(96)00018-5
   PubMedGoogle Scholar
• Iwatsubo, T., Takagi-Niidome, S., Tominaga, A., Cai, T., & Tomita, T. (2016). Conformational changes in transmembrane domain 4 of presenilin 1 are associated with altered amyloid-42 production. Journal of Neuroscience, 36(4), 1362–1372. doi:10.1523/jneurosci.5090-14.2016
   PubMed Web of Science ®Google Scholar
• Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008). CHARMM-GUI: A web-based graphical user interface for CHARMM. Journal of Computational Chemistry, 29(11), 1859–1865. doi:10.1002/jcc.20945
   PubMed Web of Science ®Google Scholar
• Kelleher, R. J., & Shen, J. (2017). Presenilin-1 mutations and Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 114(4), 629–631. doi:10.1073/pnas.1619574114
   PubMed Web of Science ®Google Scholar
• Kepp, K. P. (2014). Computing stability effects of mutations in human superoxide dismutase 1. The Journal of Physical Chemistry B, 118(7), 1799–1812. doi:10.1021/jp4119138
   PubMed Web of Science ®Google Scholar
• Kepp, K. P. (2015). Towards a “Golden Standard” for computing globin stability: Stability and structure sensitivity of myoglobin mutants. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1854(10), 1239–1248. doi:10.1016/j.bbapap.2015.06.002
   PubMed Web of Science ®Google Scholar
• Kepp, K. P. (2016). Ten challenges of the amyloid hypothesis of Alzheimer’s disease. Journal of Alzheimer's Disease, 55(2), 447–457. doi:10.3233/JAD-160550
   Web of Science ®Google Scholar
• Khachaturian, Z. S. (1987). Hypothesis on the regulation of cytosol calcium concentration and the aging brain. Neurobiology of Aging, 8(4), 345–346. doi:10.1016/0197-4580(87)90073-X
   PubMed Web of Science ®Google Scholar
• Khan, S., & Vihinen, M. (2010). Performance of protein stability predictors. Human Mutation, 31(6), 675–684. doi:10.1002/humu.21242
   PubMed Web of Science ®Google Scholar
• Knappenberger, K. S., Tian, G., Ye, X., Sobotka-Briner, C., Ghanekar, S. V., Greenberg, B. D., & Scott, C. W. (2004). Mechanism of γ-secretase cleavage activation: Is γ-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop?. Biochemistry, 43(20), 6208–6218. doi:10.1021/bi036072v
   PubMed Web of Science ®Google Scholar
• Kong, R., Chang, S., Xia, W., & Wong, S. T. C. (2015). Molecular dynamics simulation study reveals potential substrate entry path into gamma-secretase/presenilin-1. Journal of Structural Biology, 191(2), 120–129. doi:10.1016/j.jsb.2015.07.001
   PubMed Web of Science ®Google Scholar
• LaFerla, F. M. (2002). Calcium dyshomeostasis and intracellular signalling in Alzheimer’s disease. Nature Reviews Neuroscience, 3(11), 862. doi:10.1038/nrn960
   PubMed Web of Science ®Google Scholar
• Lai, M.-T., Chen, E., Crouthamel, M.-C., DiMuzio-Mower, J., Xu, M., Huang, Q., … Li, Y.-M. (2003). Presenilin-1 and presenilin-2 exhibit distinct yet overlapping γ-secretase activities. Journal of Biological Chemistry, 278(25), 22475–22481. doi:10.1074/jbc.M300974200
   PubMed Web of Science ®Google Scholar
• Laimer, J., Hofer, H., Fritz, M., Wegenkittl, S., & Lackner, P. (2015). MAESTRO - multi agent stability prediction upon point mutations. BMC Bioinformatics, 16(1), 116. doi:10.1186/s12859-015-0548-6
   PubMedGoogle Scholar
• Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M., & IUCr. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. Journal of Applied Crystallography, 26(2), 283–291. doi:10.1107/S0021889892009944
   Web of Science ®Google Scholar
• Lee, M. K., Slunt, H. H., Martin, L. J., Thinakaran, G., Kim, G., Gandy, S. E., … Sisodia, S. S. (1996). Expression of presenilin 1 and 2 (PS1 and PS2) in human and murine tissues. The Journal of Neuroscience, 16(23), 7513–7525. doi:10.1523/JNEUROSCI.16-23-07513.1996
   PubMed Web of Science ®Google Scholar
• Leissring, M. A., Akbari, Y., Fanger, C. M., Cahalan, M. D., Mattson, M. P., & LaFerla, F. M. (2000). Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice. The Journal of Cell Biology, 149(4), 793–798. doi:10.1083/jcb.149.4.793
   PubMed Web of Science ®Google Scholar
• Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D., Oshima, J., Pettingell, W., … Al, E. … (1995). Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science, 269(5226), 973–977. doi:10.1126/science.7638622
   PubMed Web of Science ®Google Scholar
• Li, X., Dang, S., Yan, C., Gong, X., Wang, J., & Shi, Y. (2013). Structure of a presenilin family intramembrane aspartate protease. Nature, 493(7430), 56–61. doi:10.1038/nature11801
   PubMed Web of Science ®Google Scholar
• Lomize, M. A., Pogozheva, I. D., Joo, H., Mosberg, H. I., & Lomize, A. L. (2012). OPM database and PPM web server: Resources for positioning of proteins in membranes. Nucleic Acids Research, 40(D1), D370–D376. doi:10.1093/nar/gkr703
   PubMed Web of Science ®Google Scholar
• Lomize, A. L., Pogozheva, I. D., Lomize, M. A., & Mosberg, H. I. (2006). Positioning of proteins in membranes: A computational approach. Protein Science, 15(6), 1318–1333. doi:10.1110/ps.062126106
   PubMed Web of Science ®Google Scholar
• Lu, P., Bai, X-C., Ma, D., Xie, T., Yan, C., Sun, L., … Shi, Y. (2014). Three-dimensional structure of human γ-secretase. Nature, 512(7513), 166–170. doi:10.1038/nature13567
   PubMed Web of Science ®Google Scholar
• Lyubartsev, A. P., & Rabinovich, A. L. (2016). Force field development for lipid membrane simulations. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1858(10), 2483–2497. doi:10.1016/J.BBAMEM.2015.12.033
   PubMed Web of Science ®Google Scholar
• Martyna, G. J., Klein, M. L., & Tuckerman, M. (1992). Nosé–Hoover chains: The canonical ensemble via continuous dynamics. The Journal of Chemical Physics, 97(4), 2635–2643. doi:10.1063/1.463940
   Web of Science ®Google Scholar
• Mattson, M. P. (2010). ER calcium and Alzheimer’s disease: In a state of flux. Science Signaling, 3(114), pe10. doi:10.1126/scisignal.3114pe10
   PubMed Web of Science ®Google Scholar
• Nelson, O., Supnet, C., Tolia, A., Horré, K., De Strooper, B., & Bezprozvanny, I. (2011). Mutagenesis mapping of the presenilin 1 calcium leak conductance pore. Journal of Biological Chemistry, 286(25), 22339–22347. doi:10.1074/jbc.M111.243063
   PubMed Web of Science ®Google Scholar
• Nichols, E., Szoeke, C. E. I., Vollset, S. E., Abbasi, N., Abd-Allah, F., Abdela, J., … Murray, C. J. L. (2019). Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(1), 88–106. doi:10.1016/S1474-4422(18)30403-4
   PubMed Web of Science ®Google Scholar
• Pandurangan, A. P., Ochoa-Montaño, B., Ascher, D. B., & Blundell, T. L. (2017). SDM: A server for predicting effects of mutations on protein stability. Nucleic Acids Research, 45(W1), W229–W235. doi:10.1093/nar/gkx439
   PubMed Web of Science ®Google Scholar
• Parrinello, M., & Rahman, A. (1981). Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics, 52(12), 7182–7190. doi:10.1063/1.328693
   Web of Science ®Google Scholar
• Pires, D. E. V., Ascher, D. B., & Blundell, T. L. (2014). DUET: A server for predicting effects of mutations on protein stability using an integrated computational approach. Nucleic Acids Research, 42(W1), gku411. doi:10.1093/nar/gku411
   Web of Science ®Google Scholar
• Pires, D. E., Ascher, D. B., & Blundell, T. L. (2014). mCSM: Predicting the effects of mutations in proteins using graph-based signatures. Bioinformatics, 30(3), 335–342. doi:10.1093/bioinformatics/btt691
   PubMed Web of Science ®Google Scholar
• Raven, F., Ward, J. F., Zoltowska, K. M., Wan, Y., Bylykbashi, E., Miller, S. J., … Zhang, C. (2017). Soluble gamma-secretase modulators attenuate Alzheimer’s β-amyloid pathology and induce conformational changes in presenilin 1. EBioMedicine, 24, 93–101. doi:10.1016/j.ebiom.2017.08.028
   PubMed Web of Science ®Google Scholar
• Rodrigues, C. H., Pires, D. E., & Ascher, D. B. (2018). DynaMut: Predicting the impact of mutations on protein conformation, flexibility and stability. Nucleic Acids Research, 46(W1), W350–W355. doi:10.1093/nar/gky300
   PubMed Web of Science ®Google Scholar
• Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., … George-Hyslop, P. H. S. (1995). Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature, 376(6543), 775–778. doi:10.1038/376775a0
   PubMed Web of Science ®Google Scholar
• Ryman, D. C., Acosta-Baena, N., Aisen, P. S., Bird, T., Danek, A., Fox, N. C., … Bateman, R. J. (2014). Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis. Neurology, 83(3), 253–260. doi:10.1212/WNL.0000000000000596
   PubMed Web of Science ®Google Scholar
• Sato, T., Diehl, T. S., Narayanan, S., Funamoto, S., Ihara, Y., De Strooper, B., … Wolfe, M. S. (2007). Active γ-secretase complexes contain only one of each component. Journal of Biological Chemistry, 282(47), 33985–33993. doi:10.1074/jbc.M705248200
   PubMed Web of Science ®Google Scholar
• Sato, C., Takagi, S., Tomita, T., & Iwatsubo, T. (2008). The C-terminal PAL motif and transmembrane domain 9 of presenilin 1 are involved in the formation of the catalytic pore of the γ-secretase. Journal of Neuroscience, 28(24), 6264–6271. doi:10.1523/JNEUROSCI.1163-08.2008
   PubMed Web of Science ®Google Scholar
• Saura, C. A., Choi, S.-Y., Beglopoulos, V., Malkani, S., Zhang, D., Rao, B. S. S., … Shen, J. (2004). Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron, 42(1), 23–36. doi:10.1016/S0896-6273(04)00182-5
   PubMed Web of Science ®Google Scholar
• Selkoe, D. J., & Hardy, J. (2016). The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Molecular Medicine, 8(6), 595–608. doi:10.15252/emmm.201606210
   PubMed Web of Science ®Google Scholar
• Shah, S., Lee, S.-F., Tabuchi, K., Hao, Y.-H., Yu, C., LaPlant, Q., … Yu, G. (2005). Nicastrin functions as a γ-secretase-substrate receptor. Cell, 122(3), 435–447. doi:10.1016/j.cell.2005.05.022
   PubMed Web of Science ®Google Scholar
• Shen, J., & Kelleher, R. J. (2007). The presenilin hypothesis of Alzheimer’s disease: Evidence for a loss-of-function pathogenic mechanism. Proceedings of the National Academy of Sciences of Sciences, 104(2), 403–409. doi:10.1073/pnas.0608332104
   PubMed Web of Science ®Google Scholar
• Shilling, D., Mak, D.-O. D., Kang, D. E., & Foskett, J. K. (2012). Lack of evidence for presenilins as endoplasmic reticulum Ca2+ leak channels. Journal of Biological Chemistry, 287(14), 10933–10944. doi:10.1074/jbc.M111.300491
   PubMed Web of Science ®Google Scholar
• Somavarapu, A. K., & Kepp, K. P. (2016a). Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer’s disease. Journal of Neurochemistry, 137(1), 101–111. doi:10.1111/jnc.13535
   PubMed Web of Science ®Google Scholar
• Somavarapu, A. K., & Kepp, K. P. (2016b). The dynamic mechanism of presenilin-1 function: Sensitive gate dynamics and loop unplugging control protein access. Neurobiology of Disease, 89, 147–156. doi:10.1016/j.nbd.2016.02.008
   PubMed Web of Science ®Google Scholar
• Somavarapu, A. K., & Kepp, K. P. (2017). Membrane dynamics of γ-secretase provides a molecular basis for β-amyloid binding and processing. ACS Chemical Neuroscience, 8(11), 2424–2436. doi:10.1021/acschemneuro.7b00208
   PubMed Web of Science ®Google Scholar
• Sun, L., Li, X., & Shi, Y. (2016). Structural biology of intramembrane proteases: Mechanistic insights from rhomboid and S2P to γ-secretase. Current Opinion in Structural Biology, 37, 97–107. doi:10.1016/J.SBI.2015.12.008
   PubMed Web of Science ®Google Scholar
• Sun, L., Zhao, L., Yang, G., Yan, C., Zhou, R., Zhou, X., … Shi, Y. (2015). Structural basis of human γ-secretase assembly. Proceedings of the National Academy of Sciences, 112(19), 6003–6008. doi:10.1073/pnas.1506242112
   PubMed Web of Science ®Google Scholar
• Sun, L., Zhou, R., Yang, G., & Shi, Y. (2017). Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proceedings of the National Academy of Sciences, 114(4), E476–E485. doi:10.1073/pnas.1618657114
   PubMed Web of Science ®Google Scholar
• Szaruga, M., Munteanu, B., Lismont, S., Veugelen, S., Horré, K., Mercken, M. … (2017). Alzheimer’s-causing mutations shift Aβ length by destabilizing γ-secretase-Aβn interactions. Cell, 170(3), 443–456. doi:10.1016/j.cell.2017.07.004
   PubMed Web of Science ®Google Scholar
• Takami, M., Nagashima, Y., Sano, Y., Ishihara, S., Morishima-Kawashima, M., Funamoto, S., & Ihara, Y. (2009). γ-Secretase: Successive tripeptide and tetrapeptide release from the transmembrane domain of β-carboxyl terminal fragment. Journal of Neuroscience, 29(41), 13042–13052. doi:10.1523/JNEUROSCI.2362-09.2009
   PubMed Web of Science ®Google Scholar
• Takeo, K., Watanabe, N., Tomita, T., & Iwatsubo, T. (2012). Contribution of the γ-secretase subunits to the formation of catalytic pore of presenilin 1 protein. Journal of Biological Chemistry, 287(31), 25834–25843. doi:10.1074/jbc.M111.336347
   PubMed Web of Science ®Google Scholar
• Tang, N., & Kepp, K. P. (2018). Aβ42/Aβ40 ratios of presenilin 1 mutations correlate with clinical onset of Alzheimer's disease. Journal of Alzheimer's Disease, 66(3), 939–945. doi:10.3233/JAD-180829
   PubMed Web of Science ®Google Scholar
• Tang, N., Somavarapu, A. K., & Kepp, K. P. (2018). Molecular recipe for γ-secretase modulation from computational analysis of 60 active compounds. ACS Omega, 3(12), 18078–18088. doi:10.1021/acsomega.8b02196
   Web of Science ®Google Scholar
• Tokuriki, N., Stricher, F., Schymkowitz, J., Serrano, L., & Tawfik, D. S. (2007). The stability effects of protein mutations appear to be universally distributed. Journal of Molecular Biology, 369(5), 1318–1332. doi:10.1016/j.jmb.2007.03.069
   PubMed Web of Science ®Google Scholar
• Tolia, A., Horré, K., & De Strooper, B. (2008). Transmembrane domain 9 of presenilin determines the dynamic conformation of the catalytic site of γ-secretase. Journal of Biological Chemistry, 283(28), 19793–19803. doi:10.1074/jbc.M802461200
   PubMed Web of Science ®Google Scholar
• Tomita, T. (2014). Molecular mechanism of intramembrane proteolysis by γ-secretase. The Journal of Biochemistry, 156(4), 195–201. doi:10.1093/jb/mvu049
   PubMed Web of Science ®Google Scholar
• Tu, H., Nelson, O., Bezprozvanny, A., Wang, Z., Lee, S.-F., Hao, Y.-H., … Bezprozvanny, I. (2006). Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations. Cell, 126(5), 981–993. doi:10.1016/j.cell.2006.06.059
   PubMed Web of Science ®Google Scholar
• Uemura, K., Lill, C. M., Li, X., Peters, J. A., Ivanov, A., Fan, Z., … Berezovska, O. (2009). Allosteric modulation of PS1/γ-secretase conformation correlates with amyloid β42/40 ratio. PLoS One, 4(11), e7893. doi:10.1371/journal.pone.0007893
   PubMed Web of Science ®Google Scholar
• Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., … Citron, M. (1999). Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science, 286(5440), 735–741. doi:10.1126/science.286.5440.735
   PubMed Web of Science ®Google Scholar
• Wahlster, L., Arimon, M., Nasser-Ghodsi, N., Post, K. L., Serrano-Pozo, A., Uemura, K., & Berezovska, O. (2013). Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer’s disease. Acta Neuropathologica, 125(2), 187–199. doi:10.1007/s00401-012-1065-6
   PubMed Web of Science ®Google Scholar
• Walker, E. S., Martinez, M., Brunkan, A. L., & Goate, A. (2005). Presenilin 2 familial Alzheimer’s disease mutations result in partial loss of function and dramatic changes in Aβ 42/40 ratios. Journal of Neurochemistry, 92(2), 294–301. doi:10.1111/j.1471-4159.2004.02858.x
   PubMed Web of Science ®Google Scholar
• Wallner, B., & Elofsson, A. (2003). Can correct protein models be identified? Protein Science, 12(5), 1073–1086. doi:10.1110/ps.0236803
   PubMed Web of Science ®Google Scholar
• Wang, J., Beher, D., Nyborg, A. C., Shearman, M. S., Golde, T. E., & Goate, A. (2006). C-terminal PAL motif of presenilin and presenilin homologues required for normal active site conformation. Journal of Neurochemistry, 96(1), 218–227. doi:10.1111/j.1471-4159.2005.03548.x
   PubMed Web of Science ®Google Scholar
• Wang, Y., Zhang, Y., & Ha, Y. (2006). Crystal structure of a rhomboid family intramembrane protease. Nature, 444(7116), 179–180. doi:10.1038/nature05255
   PubMed Web of Science ®Google Scholar
• Watanabe, N., Takagi, S., Tominaga, A., Tomita, T., & Iwatsubo, T. (2010). Functional analysis of the transmembrane domains of presenilin 1: Participation of transmembrane domains 2 and 6 in the formation of initial substrate-binding site of γ-secretase. Journal of Biological Chemistry, 285(26), 19738–19746. doi:10.1074/jbc.M110.101287
   PubMed Web of Science ®Google Scholar
• Webb, B., & Sali, A. (2017). Protein structure modeling with MODELLER. In Kihara D. (Ed.), Protein Structure Prediction. Methods in Molecular Biology (Methods and Protocols) (3rd ed., Vol. 1137, pp. 39-54). New York, NY: Humana Press. https://link.springer.com/protocol/10.1007%2F978-1-4939-0366-5_1#citeas
   Google Scholar
• Wiederstein, M., & Sippl, M. J. (2007). ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Research, 35(Web Server), W407–410. doi:10.1093/nar/gkm290
   PubMed Web of Science ®Google Scholar
• Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., & Selkoe, D. J. (1999). Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature, 398(6727), 513–517. doi:10.1038/19077
   PubMed Web of Science ®Google Scholar
• Worth, C. L., Preissner, R., & Blundell, T. L. (2011). SDM–a server for predicting effects of mutations on protein stability and malfunction. Nucleic Acids Research, 39(suppl), W215–W222. doi:10.1093/nar/gkr363
   PubMedGoogle Scholar
• Yang, G., Zhou, R., Zhou, Q., Guo, X., Yan, C., Ke, M., … Shi, Y. (2019). Structural basis of Notch recognition by human γ-secretase. Nature, 565(7738), 192–197. doi:10.1038/s41586-018-0813-8
   PubMed Web of Science ®Google Scholar
• Zampese, E., Fasolato, C., Kipanyula, M. J., Bortolozzi, M., Pozzan, T., & Pizzo, P. (2011). Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk. Proceedings of the National Academy of Sciences, 108(7), 2777–2782. doi:10.1073/pnas.1100735108
   PubMed Web of Science ®Google Scholar
• Zatti, G., Burgo, A., Giacomello, M., Barbiero, L., Ghidoni, R., Sinigaglia, G., … Fasolato, C. (2006). Presenilin mutations linked to familial Alzheimer’s disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium, 39(6), 539–550. doi:10.1016/j.ceca.2006.03.002
   PubMed Web of Science ®Google Scholar
• Zhang, Y., & Cremer, P. S. (2006). Interactions between macromolecules and ions: The Hofmeister series. Current Opinion in Chemical Biology, 10(6), 658–663. doi:10.1016/j.cbpa.2006.09.020
   PubMed Web of Science ®Google Scholar
• Zhang, H., Sun, S., Herreman, A., De Strooper, B., & Bezprozvanny, I. (2010). Role of presenilins in neuronal calcium homeostasis. Journal of Neuroscience, 30(25), 8566–8580. doi:10.1523/JNEUROSCI.1554-10.2010
   PubMed Web of Science ®Google Scholar
• Zhou, R., Yang, G., Guo, X., Zhou, Q., Lei, J., & Shi, Y. (2019). Recognition of the amyloid precursor protein by human γ-secretase. Science, 363(6428), eaaw0930. doi:10.1126/science.aaw0930
   PubMed Web of Science ®Google Scholar
• Zhuang, X., Dávila-Contreras, E. M., Beaven, A. H., Im, W., & Klauda, J. B. (2016). An extensive simulation study of lipid bilayer properties with different head groups, acyl chain lengths, and chain saturations. Biochimica et Biophysica Acta (Bba) - Biomembranes, 1858(12), 3093–3104. doi:10.1016/j.bbamem.2016.09.016
   PubMed Web of Science ®Google Scholar
• Zhuang, X., Makover, J. R., Im, W., & Klauda, J. B. (2014). A systematic molecular dynamics simulation study of temperature dependent bilayer structural properties. Biochimica et Biophysica Acta - Biomembranes, 1838(10), 2520–2529. doi:10.1016/j.bbamem.2014.06.010
   Web of Science ®Google Scholar