The ultrastructure of infectious L-type bovine spongiform encephalopathy prions constrains molecular models.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
02
02
2021
accepted:
10
05
2021
revised:
11
06
2021
pubmed:
2
6
2021
medline:
8
10
2021
entrez:
1
6
2021
Statut:
epublish
Résumé
Bovine spongiform encephalopathy (BSE) is a prion disease of cattle that is caused by the misfolding of the cellular prion protein (PrPC) into an infectious conformation (PrPSc). PrPC is a predominantly α-helical membrane protein that misfolds into a β-sheet rich, infectious state, which has a high propensity to self-assemble into amyloid fibrils. Three strains of BSE prions can cause prion disease in cattle, including classical BSE (C-type) and two atypical strains, named L-type and H-type BSE. To date, there is no detailed information available about the structure of any of the infectious BSE prion strains. In this study, we purified L-type BSE prions from transgenic mouse brains and investigated their biochemical and ultrastructural characteristics using electron microscopy, image processing, and immunogold labeling techniques. By using phosphotungstate anions (PTA) to precipitate PrPSc combined with sucrose gradient centrifugation, a high yield of proteinase K-resistant BSE amyloid fibrils was obtained. A morphological examination using electron microscopy, two-dimensional class averages, and three-dimensional reconstructions revealed two structural classes of L-type BSE amyloid fibrils; fibrils that consisted of two protofilaments with a central gap and an average width of 22.5 nm and one-protofilament fibrils that were 10.6 nm wide. The one-protofilament fibrils were found to be more abundant compared to the thicker two-protofilament fibrils. Both fibrillar assemblies were successfully decorated with monoclonal antibodies against N- and C-terminal epitopes of PrP using immunogold-labeling techniques, confirming the presence of polypeptides that span residues 100-110 to 227-237. The fact that the one-protofilament fibrils contain both N- and C-terminal PrP epitopes constrains molecular models for the structure of the infectious conformer in favour of a compact four-rung β-solenoid fold.
Identifiants
pubmed: 34061899
doi: 10.1371/journal.ppat.1009628
pii: PPATHOGENS-D-21-00233
pmc: PMC8195424
doi:
Substances chimiques
PrPSc Proteins
0
Banques de données
figshare
['10.6084/m9.figshare.14600310', '10.6084/m9.figshare.14600307']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009628Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Open Biol. 2016 May;6(5):
pubmed: 27249641
Annu Rev Pathol. 2008;3:11-40
pubmed: 18233951
Am J Epidemiol. 1997 Jun 1;145(11):959-69
pubmed: 9169904
Virus Res. 2015 Sep 2;207:120-6
pubmed: 25816779
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83
pubmed: 9811807
Neurobiol Aging. 2009 Dec;30(12):2031-42
pubmed: 18394757
Vet Rec. 1987 Oct 31;121(18):419-20
pubmed: 3424605
Brain. 2020 May 1;143(5):1512-1524
pubmed: 32303068
Biol Chem. 2005 Jun;386(6):569-80
pubmed: 16006244
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3740-5
pubmed: 19223590
PLoS Pathog. 2017 Jul 6;13(7):e1006323
pubmed: 28683090
Sci Rep. 2019 Jan 23;9(1):376
pubmed: 30675000
J Biol Chem. 2014 Aug 29;289(35):24129-42
pubmed: 25028516
J Gen Virol. 1991 Jan;72 ( Pt 1):201-4
pubmed: 1671225
Peptides. 2013 Feb;40:49-56
pubmed: 23262353
J Struct Biol. 1999 Dec 1;128(1):82-97
pubmed: 10600563
Arch Biochem Biophys. 2007 Nov 15;467(2):239-48
pubmed: 17935686
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3065-70
pubmed: 14970340
PLoS One. 2010 May 14;5(5):e10638
pubmed: 20498835
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16990-5
pubmed: 19805070
EMBO Rep. 2004 Jan;5(1):110-5
pubmed: 14710195
Pathogens. 2018 Feb 07;7(1):
pubmed: 29414853
Nat Biotechnol. 2002 Nov;20(11):1147-50
pubmed: 12389035
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8342-7
pubmed: 15155909
Prion. 2019 Jan;13(1):46-52
pubmed: 30646817
Science. 2005 Jun 3;308(5727):1435-9
pubmed: 15933194
Cell. 1983 Dec;35(2 Pt 1):349-58
pubmed: 6418385
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8334-9
pubmed: 10899999
Acta Neuropathol Commun. 2018 Apr 24;6(1):30
pubmed: 29699569
Nature. 1996 Jul 11;382(6587):180-2
pubmed: 8700211
Prion. 2014 Jan-Feb;8(1):60-6
pubmed: 24583975
J Struct Biol. 1996 Jan-Feb;116(1):17-24
pubmed: 8742718
EMBO Mol Med. 2020 Sep 7;12(9):e12739
pubmed: 32776637
Nat Med. 1998 Oct;4(10):1157-65
pubmed: 9771749
Front Bioeng Biotechnol. 2020 Oct 06;8:590501
pubmed: 33123520
PLoS Pathog. 2016 Sep 08;12(9):e1005835
pubmed: 27606840
Pathogens. 2018 May 04;7(2):
pubmed: 29734684
Biol Proced Online. 2004;6:23-34
pubmed: 15103397
Adv Protein Chem. 2006;73:55-96
pubmed: 17190611
Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):18946-51
pubmed: 18025469
J Clin Microbiol. 2007 Jun;45(6):1821-9
pubmed: 17442800
BMC Vet Res. 2012 Mar 08;8:22
pubmed: 22401036
J Struct Biol. 1996 Jan-Feb;116(1):190-9
pubmed: 8742743
Biochemistry. 1991 Aug 6;30(31):7672-80
pubmed: 1678278
J Biol Chem. 1998 Nov 27;273(48):32230-5
pubmed: 9822701
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3563-8
pubmed: 11891310
PLoS Pathog. 2019 Jul 11;15(7):e1007864
pubmed: 31295325
Vet Rec. 1991 Mar 2;128(9):199-203
pubmed: 1823120
PLoS Pathog. 2017 Apr 13;13(4):e1006229
pubmed: 28406976
Nat Struct Mol Biol. 2020 Jun;27(6):598-602
pubmed: 32514176
Nat Struct Biol. 2001 Sep;8(9):770-4
pubmed: 11524679
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14279-84
pubmed: 9405603
Nat Struct Mol Biol. 2011 Apr;18(4):504-6
pubmed: 21441913
ACS Chem Biol. 2015 May 15;10(5):1269-77
pubmed: 25695325