Alpha Synuclein only Forms Fibrils In Vitro when Larger than its Critical Size of 70 Monomers.
fibrils
protein aggregation
single molecule AFM
single molecule fluorescence
α-synuclein
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
revised:
10
08
2021
received:
11
06
2021
pubmed:
13
8
2021
medline:
22
2
2022
entrez:
12
8
2021
Statut:
ppublish
Résumé
The aggregation of α-synuclein into small soluble aggregates and then fibrils is important in the development and spreading of aggregates through the brain in Parkinson's disease. Fibrillar aggregates can grow by monomer addition and then break into fragments that could spread into neighboring cells. The rate constants for fibril elongation and fragmentation have been measured but it is not known how large an aggregate needs to be before fibril formation is thermodynamically favorable. This critical size is an important parameter controlling at what stage in an aggregation reaction fibrils can form and replicate. We determined this value to be approximately 70 monomers using super-resolution and atomic force microscopy imaging of individual α-synuclein aggregates formed in solution over long time periods. This represents the minimum size for a stable α-synuclein fibril and we hypothesis the formation of aggregates of this size in a cell represents a tipping point at which rapid replication occurs.
Identifiants
pubmed: 34383993
doi: 10.1002/cbic.202100285
pmc: PMC8518629
doi:
Substances chimiques
Amyloid
0
Protein Aggregates
0
SNCA protein, human
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2867-2871Subventions
Organisme : UK Dementia Research Institute
Organisme : DRI Ltd.
Organisme : UK Medical Research Council
Organisme : Alzheimer's Research UK
Organisme : Royal Society
Organisme : Herchel Smith Postdoctoral Research Fellowship
Organisme : Alzheimer's Society
Pays : United Kingdom
Organisme : European Research Council
ID : 669237
Pays : International
Informations de copyright
© 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH.
Références
Commun Biol. 2021 May 21;4(1):613
pubmed: 34021258
Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1206-15
pubmed: 26884195
Nat Struct Mol Biol. 2020 Oct;27(10):886-891
pubmed: 32778821
Curr Opin Neurobiol. 2020 Apr;61:58-64
pubmed: 32092527
Nature. 2005 Sep 8;437(7056):257-61
pubmed: 16148934
Anal Chem. 2012 Jul 3;84(13):5542-7
pubmed: 22697251
Chem Sci. 2017 Oct 1;8(10):7087-7097
pubmed: 29147538
J Biol Chem. 2020 May 8;295(19):6652-6664
pubmed: 32209651
J Am Chem Soc. 2018 Nov 7;140(44):14789-14798
pubmed: 30351023
Chembiochem. 2018 Oct 4;19(19):2033-2038
pubmed: 30051958
Elife. 2019 Feb 04;8:
pubmed: 30716021
J Chem Phys. 2011 Aug 14;135(6):065105
pubmed: 21842954
J Am Chem Soc. 2005 Jan 19;127(2):476-7
pubmed: 15643843
Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7230-7235
pubmed: 29941606
ACS Chem Neurosci. 2018 Jun 20;9(6):1276-1282
pubmed: 29590529
Cell. 2012 May 25;149(5):1048-59
pubmed: 22632969
Chembiochem. 2021 Oct 1;22(19):2867-2871
pubmed: 34383993