title: Amyloids and yeast prion biology.
abstract: The prions (infectious proteins) of Saccharomyces cerevisiae are proteins acting as genes, by templating their conformation from one molecule to another in analogy to DNA templating its sequence. Most yeast prions are amyloid forms of normally soluble proteins, and a single protein sequence can have any of several self-propagating forms (called prion strains or variants), analogous to the different possible alleles of a DNA gene. A central issue in prion biology is the structural basis of this conformational templating process. The in-register parallel β sheet structure found for several infectious yeast prion amyloids naturally suggests an explanation for this conformational templating. While most prions are plainly diseases, the [Het-s] prion of Podospora anserina may be a functional amyloid, with important structural implications. Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. We also review studies of the roles of chaperones, aggregate-collecting proteins, and other cellular components using yeast that have led the way in improving the understanding of similar processes that must be operating in many human amyloidoses.
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. wickner@helix.nih.gov
authors: Reed B
authors: RB
authors: Wickner
authors: Herman K
authors: HK
authors: Edskes
authors: David A
authors: DA
authors: Bateman
authors: Amy C
authors: AC
authors: Kelly
authors: Anton
authors: A
authors: Gorkovskiy
authors: Yaron
authors: Y
authors: Dayani
authors: Albert
authors: A
authors: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005658:Fungi / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005800:Genes, Fungal; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; D011328:Prions
references: Nature. 2004 Mar 18;428(6980):319-23
references: 15029195
references: Mol Biol Cell. 2012 Aug;23(16):3041-56
references: 22718905
references: Nat Cell Biol. 2008 Sep;10(9):1069-75
references: 19160487
references: Mol Gen Genet. 1986 Dec;205(3):417-21
references: 3550381
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12503-8
references: 9356479
references: J Struct Biol. 2003 Feb;141(2):132-42
references: 12615539
references: Genes Dev. 2007 Oct 1;21(19):2410-21
references: 17908928
references: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6616-21
references: 12719532
references: Mol Microbiol. 2009 Sep;73(6):1101-14
references: 19682262
references: Mol Cell Biol. 2012 Dec;32(24):4960-70
references: 23045389
references: Genetics. 2012 Feb;190(2):569-79
references: 22095075
references: Mol Microbiol. 2001 Jun;40(6):1357-69
references: 11442834
references: Mol Cell. 2001 Jun;7(6):1121-30
references: 11430816
references: EMBO J. 2002 Aug 1;21(15):4114-24
references: 12145211
references: Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4957-62
references: 18344325
references: Genetics. 1976 Oct;84(2):311-7
references: 793924
references: J Biol Chem. 2011 Aug 26;286(34):29691-9
references: 21730048
references: Nature. 1967 Sep 2;215(5105):1043-4
references: 4964084
references: FASEB J. 2007 Jun;21(8):1915-25
references: 17341688
references: J Biol Chem. 2004 Oct 29;279(44):45693-700
references: 15337765
references: Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6519-24
references: 22474356
references: Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5337-41
references: 21402947
references: Curr Microbiol. 2001 Jul;43(1):7-10
references: 11375656
references: Genetics. 1996 Dec;144(4):1375-86
references: 8978027
references: Science. 2008 Mar 14;319(5869):1523-6
references: 18339938
references: Genetics. 2011 May;188(1):81-90
references: 21368275
references: Science. 2010 Feb 12;327(5967):869-72
references: 20044542
references: Nat Rev Mol Cell Biol. 2010 Aug;11(8):579-92
references: 20651708
references: Science. 2012 Apr 20;336(6079):355-9
references: 22517861
references: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13665-70
references: 21808014
references: Genome Biol. 2009;10(9):R95
references: 19751518
references: J Biol Chem. 2003 Dec 5;278(49):49636-43
references: 14507919
references: Science. 2003 Apr 25;300(5619):640-3
references: 12690204
references: J Biol Chem. 2001 Sep 21;276(38):35227-30
references: 11473105
references: Yeast. 2011 May;28(5):349-61
references: 21341307
references: Annu Rev Phys Chem. 2011;62:279-99
references: 21219138
references: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16596-601
references: 18955697
references: Biochemistry. 2007 Nov 13;46(45):13149-62
references: 17953455
references: FEMS Yeast Res. 2011 Feb;11(1):151-3
references: 21235712
references: Genetics. 1994 Jul;137(3):671-6
references: 8088512
references: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10165-70
references: 16006506
references: Genetics. 2003 Dec;165(4):1675-85
references: 14704158
references: EMBO J. 2005 Sep 7;24(17):3082-92
references: 16096644
references: J Bacteriol. 2000 Nov;182(22):6418-23
references: 11053386
references: J Biol Chem. 1999 May 7;274(19):13666-74
references: 10224139
references: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19754-9
references: 17170131
references: Nature. 2005 Jun 9;435(7043):773-8
references: 15944695
references: J Mol Biol. 2007 Jan 19;365(3):773-82
references: 17097676
references: J Biol Chem. 1999 Jun 11;274(24):16677-80
references: 10358005
references: Trends Mol Med. 2010 Nov;16(11):501-7
references: 20870462
references: Mol Cell Biol. 1999 Dec;19(12):8103-12
references: 10567536
references: Mol Biol Cell. 2003 Aug;14(8):3449-58
references: 12925776
references: Emerg Infect Dis. 2012 Mar;18(3):369-76
references: 22377159
references: J Mol Biol. 2011 Jun 3;409(2):263-77
references: 21497604
references: Prion. 2011 Oct-Dec;5(4):317-22
references: 22156729
references: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13345-50
references: 18757753
references: Curr Biol. 2001 Mar 6;11(5):366-9
references: 11267875
references: PLoS One. 2011;6(7):e21953
references: 21760933
references: Prion. 2009 Apr-Jun;3(2):65-73
references: 19556854
references: Semin Cell Dev Biol. 2011 Jul;22(5):460-8
references: 21334447
references: Mol Cell Biol. 2006 Jan;26(2):617-29
references: 16382152
references: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13407-12
references: 9811813
references: Mol Cell Biol. 2010 Jul;30(14):3542-52
references: 20479121
references: Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):61-6
references: 10618371
references: Genetics. 2007 Jul;176(3):1557-65
references: 17507672
references: Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10432-7
references: 22691498
references: Genetics. 1982 Dec;102(4):679-90
references: 6764902
references: Yeast. 2010 Mar;27(3):167-79
references: 20014008
references: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9936-41
references: 12105276
references: J Cell Biol. 2011 Nov 14;195(4):617-29
references: 22065637
references: Mol Cell Biol. 2010 Jan;30(1):319-32
references: 19884345
references: Genetics. 2012 Sep;192(1):185-93
references: 22732191
references: Nature. 2005 Jun 9;435(7043):765-72
references: 15944694
references: PLoS Biol. 2004 Oct;2(10):e321
references: 15383837
references: Mol Microbiol. 2012 Dec;86(6):1531-47
references: 23078282
references: PLoS Genet. 2013;9(1):e1003257
references: 23382698
references: J Biol Chem. 2004 Dec 10;279(50):52319-23
references: 15448141
references: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2403-8
references: 18268327
references: Genetics. 2011 Jul;188(3):565-77
references: 21555396
references: Nature. 2008 Aug 28;454(7208):1088-95
references: 18756251
references: Genetics. 1997 Oct;147(2):507-19
references: 9335589
references: Nature. 2001 Mar 8;410(6825):165-6
references: 11242064
references: Biophys J. 2011 Nov 16;101(10):2485-92
references: 22098747
references: Science. 1994 Apr 22;264(5158):566-9
references: 7909170
references: Cell. 1998 Jul 10;94(1):73-82
references: 9674429
references: Genes Dev. 1999 Oct 1;13(19):2570-80
references: 10521401
references: Cell. 2001 Jul 27;106(2):183-94
references: 11511346
references: Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):E2683-90
references: 22949655
references: Science. 2007 Nov 9;318(5852):930-6
references: 17991853
references: BMC Biol. 2009 May 26;7:26
references: 19470166
references: J Mol Biol. 2009 Nov 20;394(1):108-18
references: 19748512
references: Yeast. 2006 Dec;23(16):1123-8
references: 17133618
references: Mol Cell Biol. 2002 Jun;22(11):3590-8
references: 11997496
references: Nat Cell Biol. 2005 Nov;7(11):1039-44
references: 16385730
references: J Struct Biol. 2005 May;150(2):170-9
references: 15866740
references: PLoS Biol. 2008 Nov 25;6(11):e294
references: 19067491
references: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8546-51
references: 22586108
references: J Cell Biol. 2012 Apr 30;197(3):369-79
references: 22529103
references: Nat Cell Biol. 2009 Mar;11(3):344-9
references: 19219034
references: Q Rev Biophys. 2006 Feb;39(1):1-55
references: 16772049
references: Cell. 2009 Apr 3;137(1):146-58
references: 19345193
references: Biochem Biophys Res Commun. 2003 Mar 14;302(3):534-8
references: 12615067
references: EMBO J. 1999 Apr 1;18(7):1974-81
references: 10202160
references: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7402-7
references: 12032295
references: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6618-22
references: 9192614
references: Nature. 2000 Sep 28;407(6803):477-83
references: 11028992
references: Biochemistry. 2005 Jan 11;44(1):321-8
references: 15628874
references: Biochemistry. 2009 Jun 16;48(23):5074-82
references: 19408895
references: Science. 2003 Mar 14;299(5613):1751-3
references: 12610228
references: Cell. 2001 Jul 27;106(2):171-82
references: 11511345
references: FEMS Yeast Res. 2010 Dec;10(8):980-91
references: 20726897
references: Mol Cell Biol. 2000 Dec;20(23):8916-22
references: 11073991
references: J Histochem Cytochem. 1968 Nov;16(11):673-7
references: 5723775
references: J Biol Chem. 2007 Jan 19;282(3):1679-86
references: 17121860
references: Semin Cell Dev Biol. 2011 Jul;22(5):469-75
references: 21345375
references: J Cell Biol. 1997 Sep 8;138(5):975-85
references: 9281577
references: Mol Microbiol. 2008 Apr;68(1):87-97
references: 18312264
references: EMBO J. 2003 May 1;22(9):2071-81
references: 12727874
references: Curr Biol. 2000 Nov 16;10(22):1443-6
references: 11102806
references: Mol Cell Biol. 2007 Jan;27(2):605-21
references: 17101785
references: Science. 1995 Oct 6;270(5233):93-5
references: 7569955
references: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12825-30
references: 16123127
references: Nature. 2004 Mar 18;428(6980):323-8
references: 15029196
references: Genetics. 2012 Aug;191(4):1107-18
references: 22595241
references: J Biol Chem. 2007 Feb 23;282(8):5545-50
references: 17178708
references: J Bacteriol. 1983 May;154(2):612-22
references: 6341357
references: J Biol Chem. 2010 May 7;285(19):14083-7
references: 20304915
references: Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10012-4
references: 9294153
references: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10575-80
references: 16024723
references: Prion. 2011 Oct-Dec;5(4):245-9
references: 22052352
references: Genes Dev. 2009 Oct 1;23(19):2320-32
references: 19797769
references: Genetics. 2002 Jan;160(1):25-36
references: 11805042
references: Nature. 2007 Sep 13;449(7159):233-7
references: 17767153
references: Curr Genet. 2006 Jan;49(1):21-9
references: 16307272
references: Nat Genet. 1999 May;22(1):55-8
references: 10319861
references: Biophys J. 2011 Nov 2;101(9):2242-50
references: 22067164
references: Mol Cell. 2000 Jan;5(1):163-72
references: 10678178
references: Mol Cell Biol. 2004 Aug;24(16):7206-13
references: 15282319
references: J Biol Chem. 2004 Jul 9;279(28):29139-46
references: 15128736
references: Nature. 2012 Feb 15;482(7385):363-8
references: 22337056
references: Genetics. 2011 Jun;188(2):339-48
references: 21467567
references: Genetics. 2009 Mar;181(3):1159-67
references: 19124570
references: Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14315-22
references: 15353587
references: Proc Natl Acad Sci U S A. 2002 Dec 10;99 Suppl 4:16384-91
references: 12177423
references: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18349-54
references: 19015532
references: EMBO J. 2008 Oct 22;27(20):2725-35
references: 18833194
references: Nat Genet. 2006 Sep;38(9):1077-81
references: 16892060
references: EMBO J. 2002 Jun 17;21(12):2903-11
references: 12065404
references: Curr Genet. 1998 Aug;34(2):146-51
references: 9724418
references: EMBO J. 1996 Jun 17;15(12):3127-34
references: 8670813
references: Mol Microbiol. 2004 Mar;51(6):1649-59
references: 15009892
references: EMBO J. 2000 Feb 1;19(3):324-31
references: 10654931
references: Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1498-503
references: 9990052
references: EMBO J. 2001 May 1;20(9):2111-9
references: 11331577
references: Yeast. 2004 Jan 30;21(2):107-17
references: 14755636
references: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14339-44
references: 19706519
references: Mol Cell Biol. 2002 Aug;22(15):5593-605
references: 12101251
references: Nat Genet. 2008 Apr;40(4):460-5
references: 18362884
references: Genetics. 1988 Mar;118(3):411-5
references: 3284783
references: Eukaryot Cell. 2013 Apr;12(4):551-8
references: 23397567
references: Ann Neurol. 2011 Oct;70(4):532-40
references: 22028219
references: Genetics. 2000 Oct;156(2):559-70
references: 11014806
references: Science. 1999 Feb 26;283(5406):1339-43
references: 10037606
references: J Bacteriol. 1971 May;106(2):519-22
references: 5573734
references: Mol Microbiol. 2000 Feb;35(4):865-76
references: 10692163
references: Genetics. 2003 Sep;165(1):23-33
references: 14504215
references: Science. 1982 Apr 9;216(4542):136-44
references: 6801762
references: Mol Cell Biol. 1987 Jan;7(1):177-84
references: 3031456
references: Cell. 2000 Jan 21;100(2):277-88
references: 10660050
references: PLoS One. 2008 May 14;3(5):e2174
references: 18478094
references: Mol Cell Biol. 1999 Feb;19(2):1325-33
references: 9891066
references: Science. 1996 Aug 2;273(5275):622-6
references: 8662547
references: Cell. 1997 May 30;89(5):811-9
references: 9182769
references: Genes Dev. 2003 Sep 1;17(17):2083-7
references: 12923060
references: J Biol Chem. 2007 Feb 2;282(5):3004-13
references: 17142456
references: Science. 1995 May 12;268(5212):880-4
references: 7754373
references: J Biol Chem. 2004 Jan 30;279(5):3361-9
references: 14610069
references: J Biol Chem. 2009 Sep 11;284(37):25065-76
references: 19574225
references: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10573-7
references: 20498075
references: J Biol Chem. 2012 Jan 2;287(1):542-556
references: 22081611
references: J Cell Biol. 2010 Jul 26;190(2):223-31
references: 20643880
references: Science. 1997 Jul 18;277(5324):381-3
references: 9219697
references: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9773-8
references: 9275200
references: Genetics. 2006 Jun;173(2):611-20
references: 16582428
references: Acc Chem Res. 2013 Jul 16;46(7):1487-96
references: 23294335
references: J Biol Chem. 2003 Oct 31;278(44):43717-27
references: 12917441