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PMID: 12649428 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Polycation-induced oligomerization and accelerated fibrillation of human alpha-synuclein in vitro.

Protein science : a publication of the Protein Society ·Vol. 12 ·No. 4 ·2003-04-00 ·Pages 702-7

Goers J, Uversky VN, Fink AL

Abstract

The aggregation and fibrillation of alpha-synuclein has been implicated as a causative factor in Parkinson's disease and several other neurodegenerative disorders known as synucleinopathies. The effect of different factors on the process of fibril formation has been intensively studied in vitro. We show here that alpha-synuclein interacts with different unstructured polycations (spermine, polylysine, polyarginine, and polyethyleneimine) to form specific complexes. In addition, the polycations catalyze alpha-synuclein oligomerization. The formation of alpha-synuclein-polycation complexes was not accompanied by significant structural changes in alpha-synuclein. However, alpha-synuclein fibrillation was dramatically accelerated in the presence of polycations. The magnitude of the accelerating effect depended on the nature of the polymer, its length, and concentration. The results illustrate the potential critical role of electrostatic interactions in protein aggregation, and the potential role of naturally occurring polycations in modulating alpha-synuclein aggregation.

MeSH Terms
Circular Dichroism Humans Microscopy, Electron Nerve Tissue Proteins/metabolism,ultrastructure Polyamines/metabolism Polyelectrolytes Polymers/metabolism Synucleins alpha-Synuclein
Chemicals
Nerve Tissue Proteins Polyamines Polyelectrolytes Polymers SNCA protein, human Synucleins alpha-Synuclein polycations
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Goers John
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Uversky Vladimir N
Fink Anthony L
References (38)
38 references, click to expand
  1. Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.
    J Mol Biol. 1999 Oct 22;293(2):321-31 PMID: 10550212
  2. Molecular modeling of protein-glycosaminoglycan interactions.
    Arteriosclerosis. 1989 Jan-Feb;9(1):21-32 PMID: 2463827
  3. Characterisation of isolated alpha-synuclein filaments from substantia nigra of Parkinson's disease brain.
    Neurosci Lett. 2000 Oct 6;292(2):128-30 PMID: 10998565
  4. Why are "natively unfolded" proteins unstructured under physiologic conditions?
    Proteins. 2000 Nov 15;41(3):415-27 PMID: 11025552
  5. Alpha-synuclein and Parkinson's disease.
    Cell Mol Life Sci. 2000 Dec;57(13-14):1894-908 PMID: 11215516
  6. Evidence for a partially folded intermediate in alpha-synuclein fibril formation.
    J Biol Chem. 2001 Apr 6;276(14):10737-44 PMID: 11152691
  7. Conformational properties of alpha-synuclein in its free and lipid-associated states.
    J Mol Biol. 2001 Apr 6;307(4):1061-73 PMID: 11286556
  8. Polyamines in the basal ganglia of human brain. Influence of aging and degenerative movement disorders.
    Neurosci Lett. 2001 May 18;304(1-2):107-11 PMID: 11335066
  9. Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism.
    Biochemistry. 2001 May 22;40(20):6036-46 PMID: 11352739
  10. Intrinsically disordered protein.
    J Mol Graph Model. 2001;19(1):26-59 PMID: 11381529
  11. Parkinson's disease and other alpha-synucleinopathies.
    Clin Chem Lab Med. 2001 Apr;39(4):308-12 PMID: 11388653
  12. Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson's disease.
    FEBS Lett. 2001 Jul 6;500(3):105-8 PMID: 11445065
  13. The protein trinity--linking function and disorder.
    Nat Biotechnol. 2001 Sep;19(9):805-6 PMID: 11533628
  14. Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein.
    Biochemistry. 2001 Sep 25;40(38):11604-13 PMID: 11560511
  15. Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure.
    J Biol Chem. 2001 Nov 23;276(47):44284-96 PMID: 11553618
  16. What does it mean to be natively unfolded?
    Eur J Biochem. 2002 Jan;269(1):2-12 PMID: 11784292
  17. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein.
    J Biol Chem. 2002 Jan 18;277(3):1641-4 PMID: 11707429
  18. Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro.
    Biochemistry. 2002 Feb 5;41(5):1502-11 PMID: 11814343
  19. Coupling of folding and binding for unstructured proteins.
    Curr Opin Struct Biol. 2002 Feb;12(1):54-60 PMID: 11839490
  20. Identification of two distinct synucleins from human brain.
    FEBS Lett. 1994 May 23;345(1):27-32 PMID: 8194594
  21. The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system.
    Neuron. 1995 Feb;14(2):467-75 PMID: 7857654
  22. NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded.
    Biochemistry. 1996 Oct 29;35(43):13709-15 PMID: 8901511
  23. Cell biology. The importance of being unfolded.
    Nature. 1997 Apr 17;386(6626):657, 659 PMID: 9109481
  24. Alpha-synuclein in Lewy bodies.
    Nature. 1997 Aug 28;388(6645):839-40 PMID: 9278044
  25. Synthetic filaments assembled from C-terminally truncated alpha-synuclein.
    FEBS Lett. 1998 Oct 9;436(3):309-12 PMID: 9801138
  26. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease.
    Nat Med. 1998 Nov;4(11):1318-20 PMID: 9809558
  27. Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro.
    J Biol Chem. 1999 Mar 19;274(12):7619-22 PMID: 10075647
  28. Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation.
    J Biol Chem. 1999 Apr 2;274(14):9843-6 PMID: 10092675
  29. Fatal attractions: abnormal protein aggregation and neuron death in Parkinson's disease and Lewy body dementia.
    Cell Death Differ. 1998 Oct;5(10):832-7 PMID: 10203692
  30. alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease.
    J Biol Chem. 1999 Jul 9;274(28):19509-12 PMID: 10391881
  31. Natively unfolded proteins: a point where biology waits for physics.
    Protein Sci. 2002 Apr;11(4):739-56 PMID: 11910019
  32. Intrinsic disorder and protein function.
    Biochemistry. 2002 May 28;41(21):6573-82 PMID: 12022860
  33. Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro.
    FEBS Lett. 2002 Apr 24;517(1-3):239-44 PMID: 12062445
  34. Identification and functions of usefully disordered proteins.
    Adv Protein Chem. 2002;62:25-49 PMID: 12418100
  35. Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson's disease.
    Neurotoxicology. 2002 Oct;23(4-5):527-36 PMID: 12428725
  36. Increased red blood cell polyamines in ALS and Parkinson's disease.
    Exp Neurol. 2002 Oct;177(2):515-20 PMID: 12429196
  37. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal.
    J Neurosci. 1988 Aug;8(8):2804-15 PMID: 3411354
  38. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):571-6 PMID: 10639120
Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
0961-8368
DOI
10.1110/ps.0230903
Published
2003-04-00
Pages
702-7
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2323845
Subset
IM
Grants
NINDS NIH HHS · NS39985 · United States
External Links
PubMed source DOI: 10.1110/ps.0230903 PMC Full Text View journal details
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