Distinct Type of Transmission Barrier Revealed by Study of Multiple Prion Determinants of Rnq1
Prions are self-propagating protein conformations. Transmission of the prion state between non-identical proteins, e.g. between homologous proteins from different species, is frequently inefficient. Transmission barriers are attributed to sequence differences in prion proteins, but their underlying mechanisms are not clear. Here we use a yeast Rnq1/[PIN+]-based experimental system to explore the nature of transmission barriers. [PIN+], the prion form of Rnq1, is common in wild and laboratory yeast strains, where it facilitates the appearance of other prions. Rnq1's prion domain carries four discrete QN-rich regions. We start by showing that Rnq1 encompasses multiple prion determinants that can independently drive amyloid formation in vitro and transmit the [PIN+] prion state in vivo. Subsequent analysis of [PIN+] transmission between Rnq1 fragments with different sets of prion determinants established that (i) one common QN-rich region is required and usually sufficient for the transmission; (ii) despite identical sequences of the common QNs, such transmissions are impeded by barriers of different strength. Existence of transmission barriers in the absence of amino acid mismatches in transmitting regions indicates that in complex prion domains multiple prion determinants act cooperatively to attain the final prion conformation, and reveals transmission barriers determined by this cooperative fold.
Vyšlo v časopise:
Distinct Type of Transmission Barrier Revealed by Study of Multiple Prion Determinants of Rnq1. PLoS Genet 6(1): e32767. doi:10.1371/journal.pgen.1000824
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000824
Souhrn
Prions are self-propagating protein conformations. Transmission of the prion state between non-identical proteins, e.g. between homologous proteins from different species, is frequently inefficient. Transmission barriers are attributed to sequence differences in prion proteins, but their underlying mechanisms are not clear. Here we use a yeast Rnq1/[PIN+]-based experimental system to explore the nature of transmission barriers. [PIN+], the prion form of Rnq1, is common in wild and laboratory yeast strains, where it facilitates the appearance of other prions. Rnq1's prion domain carries four discrete QN-rich regions. We start by showing that Rnq1 encompasses multiple prion determinants that can independently drive amyloid formation in vitro and transmit the [PIN+] prion state in vivo. Subsequent analysis of [PIN+] transmission between Rnq1 fragments with different sets of prion determinants established that (i) one common QN-rich region is required and usually sufficient for the transmission; (ii) despite identical sequences of the common QNs, such transmissions are impeded by barriers of different strength. Existence of transmission barriers in the absence of amino acid mismatches in transmitting regions indicates that in complex prion domains multiple prion determinants act cooperatively to attain the final prion conformation, and reveals transmission barriers determined by this cooperative fold.
Zdroje
1. ChitiF
DobsonCM
2006 Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75 333 366
2. EisenbergD
NelsonR
SawayaMR
BalbirinieM
SambashivanS
2006 The structural biology of protein aggregation diseases: fundamental questions and some answers. Acc Chem Res 39 568 575
3. BarnhartM
ChapmanMR
2006 Curli biogenesis and function. Annu Rev Microbiol 60 131 147
4. SaupeSJ
2007 A short story of small s: a prion of the fugus Podospora anserina.
ChernoffYO
Protein-based inheritance Austin, Texas Landes Bioscience 30 38
5. FowlerDM
KoulovAV
Alory-JostC
MarksM
BalchWE
2006 Functional amyloid formation within mammalian tissue. PLoS Biol 4 e6 doi:10.1371/journal.pbio.0040006
6. CollingeJ
ClarkeAR
2007 A general model for prion strains and their pathogenicity. Science 318 930 936
7. PrusinerSB
1982 Novel proteinaceous infectious particles cause scrapie. Science 216 136 144
8. SotoC
EstradaL
CastillaJ
2006 Amyloids, prions and the inherent infectious nature of misfolded protein aggregates. Trends Biochem Sci 31 150 155
9. WalkerLC
LeVineH
MattsonMP
JuckerM
2006 Inducible proteopathies. Trends Neurosci 29 438 443
10. WicknerRB
EdskesHK
ShewmakerF
NakayashikiT
2007 Prions of fungi: inherited structures and biological roles. Nat Rev Microbiol 5 611 618
11. WicknerRB
1994 [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science 264 566 569
12. TanakaM
ChienP
NaberN
CookeR
WeissmanJS
2004 Conformational variations in an infectious protein determine prion strain differences. Nature 428 323 328
13. KingCY
Diaz-AvalosR
2004 Protein-only transmission of three yeast prions. Nature 428 319 323
14. BrachmannA
BaxaU
WicknerRB
2005 Prion generation in vitro: amyloid of Ure2p is infectious. EMBO J 24 3082 3092
15. PatelBK
LiebmanSW
2007 “Prion-proof” for [PIN+]: infection with in vitro-made amyloid aggregates of Rnq1p-(132–405) induces [PIN+]. J Mol Biol 365 773 782
16. DuZ
ParkKW
YuH
FanQ
LiL
2008 Newly identified prion linked to chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae. Nat Genet 40 460 465
17. ChernoffYO
DerkachIL
Inge-VechtomovSG
1993 Multicopy SUP35 gene induces de novo appearance of psi-like factors in the yeast Saccharomyces cerevisiae. Curr Genet 24 268 270
18. DerkatchIL
ChernoffYO
KushnirovVV
Inge-VechtomovSG
LiebmanSW
1996 Genesis and variability of [PSI+] prion factors in Saccharomyces cerevisiae. Genetics 144 1375 1386
19. DerkatchIL
BradleyME
HongJ
LiebmanSW
2001 Prions affect the appearance of other prions: the story of [PIN+]. Cell 106 171 182
20. FiroozanM
GrantCM
DuarteJA
TuiteMF
1991 Quantitation of readthrough of termination codons in yeast using a novel gene fusion assay. Yeast 7 173 183
21. CoxBS
1965 Psi, a cytoplasmic suppressor of super-supression in yeasts. Heredity 20 505 521
22. TrueH
LindquistSL
2000 A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407 477 483
23. TrueHL
BerlinI
LindquistSL
2004 Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431 184 187
24. NakayashikiT
KurtzmanCP
EdskesHK
WicknerRB
2005 Yeast prions [URE3] and [PSI+] are diseases. Proc Natl Acad Sci USA 102 10575 10580
25. NamyO
GalopierA
MartiniC
MatsufujiS
FabretC
2008 Epigenetic control of polyamines by the prion [PSI+]. Nat Cell Biol 10 1069 1075
26. ResendeCG
OuteiroTF
SandsL
LindquistS
TuiteMF
2003 Prion protein gene polymorphisms in Saccharomyces cerevisiae. Mol Microbiol 49 1005 1017
27. EaglestoneSS
CoxBS
TuiteMF
1999 Translation efficiency can be regulated in Saccharomyces cerevisiae by environmental stress through a prion-mediated mechanism. EMBO J 18 1974 81
28. ShewmakerF
MullL
NakayashikiT
MasisonDC
WicknerRB
2007 Ure2p function is enhanced by its prion domain in Saccharomyces cerevisiae. Genetics 3 1557 65
29. HosadaN
KobayashiT
UchidaN
FunakoshiY
KikuchiY
2003 J Biol Chem 278 38287 91
30. TalarekN
MailletL
CullinC
AigleM
2005 The [URE3] prion is not conserved among Saccharomyces species. Genetics 171 23 34
31. MasisonDC
WicknerRB
1995 Prion-inducing domain of yeast Ure2p and protease-resistance of Ure2p in prion-containing cells. Science 270 93 95
32. Ter-AvanesyanMD
DagkesamanskayaAR
KushnirovVV
SmirnovVN
1994 The SUP35 omnipotent suppressor gene is involved in the maintenance of the non-Mendelian determinant [psi+] in the yeast Saccharomyces cerevisiae. Genetics 137 671 676
33. SondheimerN
LindquistS
2000 Rnq1: an epigenetic modifier of protein function in yeast. Mol Cell 5 163 172
34. TessierPM
LindquistSL
2007 Prion recognition elements govern nucleation, strain specificity and species barriers. Nature 447 556 562
35. NelsonR
SawayaMR
BalbirnieM
MadsenAO
RiekelC
2005 Structure of the cross-beta spine of amyloid-like fibrils. Nature 435 773 8
36. DePaceAH
SantosoA
HillnerP
WeissmanJS
1998 A critical role for amino-terminal glutamine/asparagine repeats in the formation and propagation of a yeast prion. Cell 93 1241 1252
37. ChenB
NewnamGP
ChernoffYO
2007 Prion species barrier between the closely related yeast proteins is detected despite co-aggregation. Proc Natl Acad Sci USA 104 2791 2796
38. KingCY
2001 Supporting the structural basis of prion strains: induction and identification of [PSI+] variants. J Mol Biol 307 1247 1260
39. ParhamSN
ResendeCG
TuiteMF
2001 Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions. EMBO J 20 2111 2119
40. OsherovichLZ
CoxBS
TuiteMF
WeissmanJS
2004 Dissection and design of yeast prions. PLoS Biol 2 e86 doi:10.1371/journal.pbio.0020086
41. ShkundinaIS
KushnirovVV
TuiteMF
Ter-AvanesyanMD
2006 The role of the N-terminal oligopeptide repeats of the yeast Sup35 prion protein in propagation and transmission of prion variants. Genetics 172 827 835
42. BruceME
FraserH
1991 Scrapie strain variation and its implications. Curr Top Microbiol Immunol 172 125 38
43. SchlumpbergerM
PrusinerSB
HerskowitzI
2001 Induction of distinct [URE3] prion strains. Mol Cell Biol 21 7035 7046
44. BradleyME
EdskesHK
HongJY
WicknerRB
LiebmanSW
2002 Interactions among prions and prion “strains” in yeast. Proc Natl Acad Sci USA 99 16392 16399
45. HillAF
DesbruslaisM
JoinerS
SidleKC
GowlandI
1997 The same prion strain causes vCJD and BSE. Nature 389 448 450
46. VanikDL
SurewiczCA
SurewiczWK
2004 Molecular basis of barriers for interspecies transmissibility of mammalian prions. Mol Cell 14 139 145
47. TanakaM
ChienP
YonekuraK
WeissmanJS
2005 Mechanism of cross-species prion transmission: an infectious conformation compatible with two highly divergent yeast prion proteins. Cell 121 49 62
48. BradleyME
LiebmanSW
2004 The Sup35 domains required for maintenance of weak, strong or undifferentiated yeast [PSI+] prions. Mol Micro 51 1649 1659
49. KrishnanR
LindquistSL
2005 Structural insights into a yeast prion illuminate nucleation and strain diversity. Nature 435 765 72
50. ToyamaBH
KellyMJS
GrossJD
WeissmanJS
2007 The structural basis of yeast prion strain variants. Nature 449 233 238
51. ChangHY
LinJY
LeeHC
WangHL
KingCY
2008 Strain-specific sequences required for yeast [PSI+] prion propagation. Proc Natl Acad Sci USA 105 13345 50
52. DerkatchIL
LiebmanSW
2007 Prion-prion interactions. Prion 1 161 169
53. DerkatchIL
BradleyME
ZhouP
ChernoffYO
LiebmanSW
1997 Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae. Genetics 147 507 519
54. DerkatchIL
BradleyME
MasseS
ZadorskySP
PolozkovGI
2000 Dependence and independence of [PSI+] and [PIN+]: a two-prion system in yeast? EMBO J 19 1942 1952
55. OsherovichLZ
WeissmanJS
2001 Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI+] prion. Cell 106 183 194
56. TanejaV
MaddeleinML
TalarekN
SaupeSJ
LiebmanSW
2007 A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast. Mol Cell 27 67 77
57. DerkatchIL
UptainSM
OuteiroTF
KrishnanR
LindquistSL
2004 Effects of Q/N, polyQ and non-polyQ amyloids on the de novo formation of the [PSI+] prion in yeast and aggregation of Sup35 in vitro. Proc Natl Acad Sci USA 101 12934 12939
58. VitrenkoYA
GrachevaEO
RichmondJE
LiebmanSW
2007 Visualization of aggregation of the Rnq1 prion domain and cross-seeding interactions with Sup35NM. J Biol Chem 282 1779 1787
59. BradleyME
LiebmanSW
2003 Destabilizing interactions among [PSI+] and [PIN+] yeast prion variants. Genetics 165 1675 1685
60. MeriinAB
ZhangX
HeX
NewnamGP
ChernoffYO
2002 Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J Cell Biol 157 997 1004
61. GokhaleKC
NewnamGP
ShermanMY
ChernoffYO
2005 Modulation of prion-dependent polyglutamine aggregation and toxicity by chaperone proteins in the yeast model. J Biol Chem 280 22809 22818
62. GanusovaEE
OzolinsLN
BhagatS
NewnamGP
WegrzynRD
2006 Modulation of prion formation, aggregation and toxicity by the actin cytoskeleton in yeast. Mol Cell Biol 26 617 629
63. MeriinAB
ZhangX
AlexandrovIM
SalnikovaAB
Ter-AvanesyanMD
2007 Endocytosis machinery is involved in aggregation of proteins with expanded polyglutamine domains. FASEB J 21 1915 1925
64. AllenKD
ChernovaTA
TennantEP
WilkinsonKD
ChernoffYO
2007 Effects of ubiquitin system alterations on the formation and loss of yeast prion. J Biol Chem 282 3004 3013
65. VitrenkoYA
PavonME
StoneSI
LiebmanSW
2007 Propagation of the [PIN+] prion by fragments of Rnq1 fused to GFP. Curr Genet 51 309 319
66. WicknerRB
DydaF
TyckoR
2008 Amyloid of Rnq1p, the basis of the [PIN+] prion, has a parallel in-register beta-sheet structure. Proc Natl Acad Sci USA 105 2403 2408
67. RostB
YachdavG
LiuJ
2004 The PredictProtein Server. Nucl Ac Res 32 W321 W326
68. DouglasPM
TreuschS
RenHY
HalfmannR
DuennwaldML
2008 Chaperone-dependent amyloid assembly protects cells from prion toxicity. Proc Natl Acad Sci USA 105 7206 7211
69. LiebmanSW
BagriantsevSN
DerkatchIL
2006 Biochemical and genetic methods for characterization of [PIN+] prions in yeast. Methods 39 23 34
70. PatinoMM
LiuJ
GloverJR
LindquistS
1996 Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science 273 622 626
71. ZhouP
DerkatchIL
LiebmanSW
2001 The relationship between visible intracellular aggregates that appear after overexpression of Sup35 and the yeast prion-like elements [PSI+] and [PIN+]. Mol Microbiol 39 37 46
72. BaskakovIV
BocharovaOV
2005 In vitro conversion of mammalian prion protein into amyloid fibrils displays unusual features. Biochemistry 44 2339 2348
73. LashuelHA
HartleyD
PetreBM
WalzT
LansburyPTJr
2002 Amyloid pores from pathogenic mutations. Nature 418 291
74. ShorterJ
LindquistS
2006 Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities. Mol Cell 23 425 438
75. AlexandrovIN
VishnevskayaAB
Ter-AvanesyanMD
KushnirovVV
2008 Appearance and propagation of polyglutamine-based amyloids in yeast: tyrosine residues enable polymer fragmentation. J Biol Chem 283 15182 15192
76. RitterC
MaddeleinML
SiemerAB
LuhrsT
ErnstM
2005 Correlation of structural elements and infectivity of the HET-s prion. Nature 435 844 848
77. GloverJR
KowalAS
SchirmerEC
PatinoMM
LiuJJ
1997 Self-seeded fibers formed by Sup35 The protein determinant of [PSI+], a prion-like factor of Saccharomyces cerevisiae. Cell 89 811 819
78. KingCY
TittmanP
GrossH
GebertR
AebiM
1997 Prion-inducing domain 2–114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments. Proc Natl Acad Sci USA 94 6618 6622
79. SolforosiL
BellonA
SchallerM
CruiteJT
AbalosGC
2007 Toward molecular dissection of PrPC-PrPSc interactions. J Biol Chem 282 7465 7471
80. OstapchenkoVG
MakaravaN
SavtchenkoR
BaskakovIV
2008 The polybasic N-terminal region of the prion protein controls the physical properties of both the cellular and fibrillar forms of PrP. J Mol Biol 383 1210 1224
81. BerthoG
BouvierG
HoaGH
GiraultJP
2008 The key-role of tyrosine 155 in the mechanism of prion transconformation as highlighted by a study of sheep mutant peptides. Peptides 29 1073 1084
82. MaddeleinML
WicknerRB
1999 Two prion-inducing regions of Ure2p are nonoverlapping. Mol Cell Biol 19 4516 4524
83. PattisonIH
1965 Experiments with scrapie with special reference to the nature of the agent and the pathology of the disease
GajdusekCJ
GibbsCJ
AlpersMP
Slow latent and temperate virus infections Washington DC NINDB US Government Printing 249 257
84. ChienP
DePaceAH
CollinsSR
WeissmanJS
2003 Generation of prion transmission barriers by mutational control of amyloid conformations. Nature 424 948 951
85. PrusinerS
ScottM
FosterD
PanK-M
GrothD
1990 Transgenic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63 673 686
86. SurewiczWK
JonesEM
ApetriAC
2006 The emerging principles of mammalian prion propagation and transmissibility barriers: Insight from studies in vitro. Acc Chem Res 39 654 662
87. LangedijkJP
FuentesG
BoshuizenR
BonvinAM
2006 Two-rung model of a left-handed beta-helix for prions explains species barrier and strain variation in transmissible spongiform encephalopathies. J Mol Biol 360 907 920
88. BishopMT
HartP
AitchisonL
BaybuttHN
PlinstonC
2006 Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 5 393 398
89. CancellottiE
BarronRM
BishopMT
HartP
WisemanF
2007 The role of host PrP in Transmissible Spongiform Encephalopathies. Biochim Biophys Acta 1772 673 680
90. GorfeAA
CaflischA
2007 Ser170 controls the conformational multiplicity of the loop 166–175 in prion proteins: implication for conversion and species barrier. FASEB J 21 3279 3287
91. ChernoffYO
LindquistSL
OnoB
Inge-VechtomovSG
LiebmanSW
1995 Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science 268 880 884
92. TuiteMF
MundyCR
CoxBS
1981 Agents that cause a high frequency of genetic change from [psi+] to [psi-] in Saccharomyces cerevisiae. Genetics 98 691 711
93. Orr-WeaverTL
SzostakJW
RothsteinRJ
1983 Genetic applications of yeast transformation with linear and gapped plasmids. Methods Enzymol 101 228 245
94. RoseMD
WinstonF
HeiterP
1990 Methods in yeast genetics Cold Spring Harbor Cold Spring Harbor Press
95. ShermanF
FinkGR
HicksJB
1986 Methods in yeast genetics Cold Spring Harbor Cold Spring Harbor Press
96. BoekeJD
TruehartJ
NatsoulisG
FinkGR
1987 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol 154 164 175
97. LopezN
AronR
CraigEA
2003 The role of Sis1 on the maintenance of [RNQ+] prion. Mol Biol Cell 14 1172 1181
98. LeVineH3rd
1999 Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309 274 284
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