Advertisement

A complete catalog of wild-type Sup35 prion variants and their protein-only propagation

  • Yu-Wen Huang
  • Chih-Yen KingEmail author
Original Article
  • 44 Downloads

Abstract

Twenty-three prion variants of the wild-type Sup35 protein are obtained, including 19 novel ones and 4 previously documented, namely, VH, VK, VL, and W8. Their uniqueness and non-composite nature are demonstrated. Specific infectivity is generated de novo for most variants by adding prion particles to solutions of a purified Sup35 N-terminal fragment, thereby supporting the protein-only composition. Sup35 prions isolated by other laboratories are identified within the collection and found to fall into a narrow set of five variant types that are readily inducible in vivo by Sup35 overexpression. The work establishes an unambiguous and extensive collection of prion variants, demonstrating that a protein, by itself, in the absence of genetic and conformational co-factors, could adopt a great number of structures. In light of recent high-resolution structures of other amyloids, we discuss how the diverse folding is achieved in spite of apparent contradiction to the classical paradigm that a protein’s structure is uniquely determined by its sequence.

Keywords

[PSI+Prion Variants Amyloid Saccharomyces cerevisiae 

Notes

Acknowledgements

We thank Drs. S. W. Liebman, M. Tanaka, and R. B. Wickner for yeast strains; Drs. V. V. Kushnirov, M. Tanaka, and R. B. Wickner for discussion; S.-P.Lee, S.-P. Tsai, and W.-L. Pong for help with imaging; T. T. Le, Y. Chen, H.-C. Lee, and C.-I. Yu for technical assistance. This work was supported by Grant 105-2311-B-001-056 from Ministry of Science and Technology, Taiwan, Republic of China.

Author contributions

Both authors designed the study, performed experiments, and wrote the manuscript.

Supplementary material

294_2019_1003_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1821 kb)

References

  1. Anfinsen CB (1973) Principles that govern the folding of protein chains. Science 181:223–230CrossRefGoogle Scholar
  2. Astbury WT, Dickinson S, Bailey K (1935) The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem J 29(2351–2360):1.  https://doi.org/10.1042/bj0292351 Google Scholar
  3. Bateman DA, Wickner RB (2013) The [PSI +] prion exists as a dynamic cloud of variants. PLoS Genet 9:e1003257.  https://doi.org/10.1371/journal.pgen.1003257 CrossRefGoogle Scholar
  4. Bradley ME, Edskes HK, Hong JY et al (2002) Interactions among prions and prion “strains” in yeast. Proc Natl Acad Sci USA 99(Suppl 4):16392–16399.  https://doi.org/10.1073/pnas.152330699 CrossRefGoogle Scholar
  5. Bruce ME (1993) Scrapie strain variation and mutation. Br Med Bull 49:822–838CrossRefGoogle Scholar
  6. Bruce ME, Boyle A, Cousens S et al (2002) Strain characterization of natural sheep scrapie and comparison with BSE. J Gen Virol 83:695–704.  https://doi.org/10.1099/0022-1317-83-3-695 CrossRefGoogle Scholar
  7. Carp RI, Callahan SM (1991) Variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep. J Gen Virol 72:293–298.  https://doi.org/10.1099/0022-1317-72-2-293 CrossRefGoogle Scholar
  8. Castilla J, Gonzalez-Romero D, Saá P et al (2008) Crossing the species barrier by PrPSc replication in vitro generates unique infectious prions. Cell 134:757–768.  https://doi.org/10.1016/j.cell.2008.07.030 CrossRefGoogle Scholar
  9. Chang H-Y, Lin J-Y, Lee H-C et al (2008) Strain-specific sequences required for yeast [PSI +] prion propagation. Proc Natl Acad Sci USA 105:13345–13350.  https://doi.org/10.1073/pnas.0802215105 CrossRefGoogle Scholar
  10. Chen B, Bruce KL, Newnam GP et al (2010) Genetic and epigenetic control of the efficiency and fidelity of cross-species prion transmission. Mol Microbiol 76:1483–1499.  https://doi.org/10.1111/j.1365-2958.2010.07177.x CrossRefGoogle Scholar
  11. Chernoff YO, Lindquist SL, Ono B et al (1995) Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi +]. Science 268:880–884CrossRefGoogle Scholar
  12. Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366.  https://doi.org/10.1146/annurev.biochem.75.101304.123901 CrossRefGoogle Scholar
  13. Clavaguera F, Bolmont T, Crowther RA et al (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11:909–913.  https://doi.org/10.1038/ncb1901 CrossRefGoogle Scholar
  14. Colby DW, Prusiner SB (2011) Prions. Cold Spring Harb Perspect Biol 3:a006833.  https://doi.org/10.1101/cshperspect.a006833 CrossRefGoogle Scholar
  15. Colvin MT, Silvers R, Ni QZ et al (2016) Atomic resolution structure of monomorphic Aβ42 amyloid fibrils. J Am Chem Soc 138:9663–9674.  https://doi.org/10.1021/jacs.6b05129 CrossRefGoogle Scholar
  16. Cox BS (1965) Ψ, A cytoplasmic suppressor of super-suppressor in yeast. Heredity 20:505CrossRefGoogle Scholar
  17. Cox B, Tuite M (2018) The life of [PSI]. Curr Genet 64:1–8.  https://doi.org/10.1007/s00294-017-0714-7 CrossRefGoogle Scholar
  18. DeArmond SJ, Qiu Y, Sànchez H et al (1999) PrPC glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains. J Neuropathol Exp Neurol 58:1000–1009CrossRefGoogle Scholar
  19. Deleault NR, Walsh DJ, Piro JR et al (2012) Cofactor molecules maintain infectious conformation and restrict strain properties in purified prions. Proc Natl Acad Sci USA 109:E1938–E1946.  https://doi.org/10.1073/pnas.1206999109 CrossRefGoogle Scholar
  20. Dergalev AA, Alexandrov AI, Ivannikov RI, et al (2019) Yeast Sup35 Prion Structure: Two Types, Four Parts, Many Variants. Int J Mol Sci 20:604660.  https://doi.org/10.3390/ijms20112633 Google Scholar
  21. Derkatch IL, Chernoff YO, Kushnirov VV et al (1996) Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics 144:1375–1386Google Scholar
  22. Derkatch IL, Bradley ME, Hong JY, Liebman SW (2001) Prions affect the appearance of other prions: the Story of [PIN+]. Cell 106:171–182CrossRefGoogle Scholar
  23. Diaz-Avalos R, King C-Y, Wall J et al (2005) Strain-specific morphologies of yeast prion amyloid fibrils. Proc Natl Acad Sci USA 102:10165–10170.  https://doi.org/10.1073/pnas.0504599102 CrossRefGoogle Scholar
  24. Falcon B, Zhang W, Murzin AG et al (2018) Structures of filaments from Pick’s disease reveal a novel tau protein fold. Nature 561:137–140.  https://doi.org/10.1038/s41586-018-0454-y CrossRefGoogle Scholar
  25. Fitzpatrick AWP, Falcon B, He S et al (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547:185–190.  https://doi.org/10.1038/nature23002 CrossRefGoogle Scholar
  26. Gietz RD, Sugino A (1988) New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene 74:527–534CrossRefGoogle Scholar
  27. Goldstein AL, McCusker JH (1999) Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast 15:1541–1553.  https://doi.org/10.1002/(SICI)1097-0061(199910)15:14%3c1541:AID-YEA476%3e3.0.CO;2-K CrossRefGoogle Scholar
  28. Gorkovskiy A, Reidy M, Masison DC, Wickner RB (2017) Hsp104 disaggregase at normal levels cures many [PSI +] prion variants in a process promoted by Sti1p, Hsp90, and Sis1p. Proc Natl Acad Sci USA 114:E4193–E4202.  https://doi.org/10.1073/pnas.1704016114 CrossRefGoogle Scholar
  29. Gremer L, Schölzel D, Schenk C et al (2017) Fibril structure of amyloid-β(1-42) by cryo-electron microscopy. Science 358:116–119.  https://doi.org/10.1126/science.aao2825 CrossRefGoogle Scholar
  30. Guerrero-Ferreira R, Taylor NM, Mona D et al (2018) Cryo-EM structure of alpha-synuclein fibrils. Elife.  https://doi.org/10.7554/elife.36402 Google Scholar
  31. Güldener U, Heck S, Fielder T et al (1996) A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 24:2519–2524CrossRefGoogle Scholar
  32. Halfmann R, Jarosz DF, Jones SK et al (2012) Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature 482:363–368.  https://doi.org/10.1038/nature10875 CrossRefGoogle Scholar
  33. Hennetin J, Jullian B, Steven AC, Kajava AV (2006) Standard conformations of β-arches in β-solenoid proteins. J Mol Biol 358:1094–1105.  https://doi.org/10.1016/j.jmb.2006.02.039 CrossRefGoogle Scholar
  34. Huang VJ, Stein KC, True HL (2013) Spontaneous variants of the [RNQ +] prion in yeast demonstrate the extensive conformational diversity possible with prion proteins. PLoS One 8:e79582.  https://doi.org/10.1371/journal.pone.0079582 CrossRefGoogle Scholar
  35. Huang Y-W, Chang Y-C, Diaz-Avalos R, King C-Y (2015) W8, a new Sup35 prion strain, transmits distinctive information with a conserved assembly scheme. Prion 9:207–227.  https://doi.org/10.1080/19336896.2015.1039217 CrossRefGoogle Scholar
  36. Kajava AV, Baxa U, Steven AC (2010) β arcades: recurring motifs in naturally occurring and disease-related amyloid fibrils. FASEB J 24:1311–1319.  https://doi.org/10.1096/fj.09-145979 CrossRefGoogle Scholar
  37. Kaufman SK, Sanders DW, Thomas TL et al (2016) Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. Neuron 92:796–812.  https://doi.org/10.1016/j.neuron.2016.09.055 CrossRefGoogle Scholar
  38. Kimberlin RH, Walker CA, Fraser H (1989) The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. J Gen Virol 70:2017–2025.  https://doi.org/10.1099/0022-1317-70-8-2017 CrossRefGoogle Scholar
  39. King C-Y (2001) Supporting the structural basis of prion strains: induction and identification of [PSI] variants. J Mol Biol 307:1247–1260.  https://doi.org/10.1006/jmbi.2001.4542 CrossRefGoogle Scholar
  40. King C-Y, Diaz-Avalos R (2004) Protein-only transmission of three yeast prion strains. Nature 428:319–323.  https://doi.org/10.1038/nature02391 CrossRefGoogle Scholar
  41. Kochneva-Pervukhova NV, Chechenova MB, Valouev IA et al (2001) [PSI +] prion generation in yeast: characterization of the “strain” difference. Yeast 18:489–497.  https://doi.org/10.1002/yea.700 CrossRefGoogle Scholar
  42. Kryndushkin DS, Alexandrov IM, Ter-Avanesyan MD, Kushnirov VV (2003) Yeast [PSI +] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104. J Biol Chem 278:49636–49643.  https://doi.org/10.1074/jbc.M307996200 CrossRefGoogle Scholar
  43. Kryndushkin D, Pripuzova N, Burnett BG, Shewmaker F (2013) Non-targeted identification of prions and amyloid-forming proteins from yeast and mammalian cells. J Biol Chem 288:27100–27111.  https://doi.org/10.1074/jbc.M113.485359 CrossRefGoogle Scholar
  44. Legname G, Baskakov IV, Nguyen H-OB et al (2004) Synthetic mammalian prions. Science 305:673–676.  https://doi.org/10.1126/science.1100195 CrossRefGoogle Scholar
  45. Li J, Browning S, Mahal SP, Oelschlegal AM, Weissmann C (2010) Darwinian evolution of prions in cell culture. Science 327:869–873CrossRefGoogle Scholar
  46. Li B, Ge P, Murray KA et al (2018) Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel. Nat Commun 9:3609.  https://doi.org/10.1038/s41467-018-05971-2 CrossRefGoogle Scholar
  47. Liberta F, Loerch S, Rennegarbe M et al (2018) Cryo-EM structure of an amyloid fibril from systemic amyloidosis. bioRxiv.  https://doi.org/10.1101/357129 Google Scholar
  48. Liebman SW, All-Robyn JA (1984) A non-Mendelian factor, [eta+], causes lethality of yeast omnipotent-suppressor strains. Curr Genet 8:567–573.  https://doi.org/10.1007/BF00395701 CrossRefGoogle Scholar
  49. Lu J-X, Qiang W, Yau W-M et al (2013) Molecular structure of β-amyloid fibrils in Alzheimer’s disease brain tissue. Cell 154:1257–1268.  https://doi.org/10.1016/j.cell.2013.08.035 CrossRefGoogle Scholar
  50. Ma J (2012) The role of cofactors in prion propagation and infectivity. PLoS Pathog 8:e1002589.  https://doi.org/10.1371/journal.ppat.1002589 CrossRefGoogle Scholar
  51. Marczynski GT, Jaehning JA (1985) A transcription map of a yeast centromere plasmid: unexpected transcripts and altered gene expression. Nucleic Acids Res 13:8487–8506.  https://doi.org/10.1093/nar/13.23.8487 CrossRefGoogle Scholar
  52. Mathur V, Hong JY, Liebman SW (2009) Ssa1 Overexpression and [PIN +] variants cure [PSI +] by dilution of aggregates. J Mol Biol 390:155–167.  https://doi.org/10.1016/j.jmb.2009.04.063 CrossRefGoogle Scholar
  53. McGlinchey RP, Kryndushkin D, Wickner RB (2011) Suicidal [PSI +] is a lethal yeast prion. Proc Natl Acad Sci USA 108:5337–5341.  https://doi.org/10.1073/pnas.1102762108 CrossRefGoogle Scholar
  54. Meier BH, Böckmann A (2015) The structure of fibrils from “misfolded” proteins. Curr Opin Struct Biol 30:43–49.  https://doi.org/10.1016/j.sbi.2014.12.001 CrossRefGoogle Scholar
  55. Meinhardt J, Sachse C, Hortschansky P et al (2009) Aβ(1-40) fibril polymorphism implies diverse interaction patterns in amyloid fibrils. J Mol Biol 386:869–877.  https://doi.org/10.1016/j.jmb.2008.11.005 CrossRefGoogle Scholar
  56. Miyazawa K, Masujin K, Matsuura Y et al (2018) Interspecies transmission to bovinized transgenic mice uncovers new features of a CH1641-like scrapie isolate. Vet Res 49:116.  https://doi.org/10.1186/s13567-018-0611-1 CrossRefGoogle Scholar
  57. Nishina KA, Deleault NR, Mahal SP et al (2006) The stoichiometry of host PrPC glycoforms modulates the efficiency of PrPSc formation in vitro. Biochemistry 45:14129–14139.  https://doi.org/10.1021/bi061526k CrossRefGoogle Scholar
  58. Ohhashi Y, Ito K, Toyama BH et al (2010) Differences in prion strain conformations result from non-native interactions in a nucleus. Nat Chem Biol 6:225–230.  https://doi.org/10.1038/nchembio.306 CrossRefGoogle Scholar
  59. Ohhashi Y, Yamaguchi Y, Kurahashi H et al (2018) Molecular basis for diversification of yeast prion strain conformation. Proc Natl Acad Sci USA 115:2389–2394.  https://doi.org/10.1073/pnas.1715483115 CrossRefGoogle Scholar
  60. Resende C, Parham SN, Tinsley C et al (2002) The Candida albicans Sup35p protein (CaSup35p): function, prion-like behaviour and an associated polyglutamine length polymorphism. Microbiology 148:1049–1060.  https://doi.org/10.1099/00221287-148-4-1049 CrossRefGoogle Scholar
  61. Saá P, Sferrazza GF, Ottenberg G et al (2012) Strain-specific role of RNAs in prion replication. J Virol 86:10494–10504.  https://doi.org/10.1128/JVI.01286-12 CrossRefGoogle Scholar
  62. Sawaya MR, Sambashivan S, Nelson R et al (2007) Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447:453–457.  https://doi.org/10.1038/nature05695 CrossRefGoogle Scholar
  63. Schmidt M, Rohou A, Lasker K et al (2015) Peptide dimer structure in an Aβ(1-42) fibril visualized with cryo-EM. Proc Natl Acad Sci USA 112:11858–11863.  https://doi.org/10.1073/pnas.1503455112 CrossRefGoogle Scholar
  64. Sharma J, Liebman SW (2012) [PSI +] prion variant establishment in yeast. Mol Microbiol 86:866–881.  https://doi.org/10.1111/mmi.12024 CrossRefGoogle Scholar
  65. Sharma J, Liebman SW (2013) Exploring the basis of [PIN +] variant differences in [PSI +] induction. J Mol Biol 425:3046–3059.  https://doi.org/10.1016/j.jmb.2013.06.006 CrossRefGoogle Scholar
  66. Sherman F (1991) Getting started with yeast. Methods Enzymol 194:3–21CrossRefGoogle Scholar
  67. Shewmaker F, Wickner RB, Tycko R (2006) Amyloid of the prion domain of Sup35p has an in-register parallel β-sheet structure. Proc Natl Acad Sci USA 103:19754–19759.  https://doi.org/10.1073/pnas.0609638103 CrossRefGoogle Scholar
  68. Skerra A, Schmidt TG (2000) Use of the Strep-Tag and streptavidin for detection and purification of recombinant proteins. Methods Enzymol 326:271–304CrossRefGoogle Scholar
  69. Supattapone S (2014) Elucidating the role of cofactors in mammalian prion propagation. Prion 8:100–105CrossRefGoogle Scholar
  70. Tanaka M, Chien P, Naber N et al (2004) Conformational variations in an infectious protein determine prion strain differences. Nature 428:323–328.  https://doi.org/10.1038/nature02392 CrossRefGoogle Scholar
  71. Tanaka M, Chien P, Yonekura K, Weissman JS (2005) Mechanism of cross-species prion transmission: an infectious conformation compatible with two highly divergent yeast prion proteins. Cell 121:49–62.  https://doi.org/10.1016/j.cell.2005.03.008 CrossRefGoogle Scholar
  72. Ter-Avanesyan MD, Dagkesamanskaya AR, Kushnirov VV, Smirnov VN (1994) The SUP35 omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [psi +] in the yeast Saccharomyces cerevisiae. Genetics 137:671–676Google Scholar
  73. Tuite MF, Staniforth GL, Cox BS (2015) [PSI +] turns 50. Prion 9:318–332.  https://doi.org/10.1080/19336896.2015.1111508 CrossRefGoogle Scholar
  74. Tuttle MD, Comellas G, Nieuwkoop AJ et al (2016) Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein. Nat Struct Mol Biol 23:409–415.  https://doi.org/10.1038/nsmb.3194 CrossRefGoogle Scholar
  75. Tycko R (2014) Physical and structural basis for polymorphism in amyloid fibrils. Protein Sci 23:1528–1539.  https://doi.org/10.1002/pro.2544 CrossRefGoogle Scholar
  76. von der Haar T (2007) Optimized protein extraction for quantitative proteomics of yeasts. PLoS One 2:e1078.  https://doi.org/10.1371/journal.pone.0001078 CrossRefGoogle Scholar
  77. Wälti MA, Ravotti F, Arai H et al (2016) Atomic-resolution structure of a disease-relevant Aβ(1-42) amyloid fibril. Proc Natl Acad Sci USA 113:E4976–E4984.  https://doi.org/10.1073/pnas.1600749113 CrossRefGoogle Scholar
  78. Wang F, Wang X, Yuan C-G, Ma J (2010) Generating a prion with bacterially expressed recombinant prion protein. Science 327:1132–1135.  https://doi.org/10.1126/science.1183748 CrossRefGoogle Scholar
  79. Wang F, Zhang Z, Wang X et al (2012) Genetic informational RNA is not required for recombinant prion infectivity. J Virol 86:1874–1876.  https://doi.org/10.1128/JVI.06216-11 CrossRefGoogle Scholar
  80. Wasmer C, Lange A, Van Melckebeke H et al (2008) Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core. Science 319:1523–1526.  https://doi.org/10.1126/science.1151839 CrossRefGoogle Scholar
  81. Westergard L, True HL (2014) Wild yeast harbour a variety of distinct amyloid structures with strong prion-inducing capabilities. Mol Microbiol 92:183–193.  https://doi.org/10.1111/mmi.12543 CrossRefGoogle Scholar
  82. Wickner RB (2016) Yeast and fungal prions. Cold Spring Harb Perspect Biol 8:1–16.  https://doi.org/10.1101/cshperspect.a023531 CrossRefGoogle Scholar
  83. Wickner RB, Kelly AC, Bezsonov EE, Edskes HK (2017) [PSI +] prion propagation is controlled by inositol polyphosphates. Proc Natl Acad Sci USA.  https://doi.org/10.1073/pnas.1714361114 Google Scholar
  84. Wickner RB, Edskes HK, Bezsonov EE et al (2018) Prion propagation and inositol polyphosphates. Curr Genet 64:571–574.  https://doi.org/10.1007/s00294-017-0788-2 CrossRefGoogle Scholar
  85. Yu C-I, King C-Y (2018) Forms and abundance of chaperone proteins influence yeast prion variant competition. Mol Microbiol.  https://doi.org/10.1111/mmi.14192 Google Scholar
  86. Zhang R, Hu X, Khant H et al (2009) Interprotofilament interactions between Alzheimer’s Aβ1-42 peptides in amyloid fibrils revealed by cryoEM. Proc Natl Acad Sci USA 106:4653–4658.  https://doi.org/10.1073/pnas.0901085106 CrossRefGoogle Scholar
  87. Zhang W, Falcon B, Murzin AG et al (2019) Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases. Elife.  https://doi.org/10.7554/elife.43584 Google Scholar
  88. Zhou P, Derkatch IL, Uptain SM et al (1999) The yeast non-Mendelian factor [ETA +] is a variant of [PSI +], a prion-like form of release factor eRF3. EMBO J 18:1182–1191.  https://doi.org/10.1093/emboj/18.5.1182 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Molecular and Cell Biology, Taiwan International Graduate ProgramAcademia Sinica and National Defense Medical CenterTaipeiTaiwan
  2. 2.Institute of Molecular BiologyAcademia SinicaTaipeiTaiwan

Personalised recommendations