Linked Life Data

19895818

Source:http://linkedlifedata.com/resource/pubmed/id/19895818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-1-28
pubmed:abstractText
alpha-Synuclein is a major component of filamentous inclusions that are histological hallmarks of Parkinson's disease and other alpha-synucleinopathies. Previous analyses have revealed that several polyphenols inhibit alpha-synuclein assembly with low micromolar IC(50) values, and that SDS-stable, noncytotoxic soluble alpha-synuclein oligomers are formed in their presence. Structural elucidation of inhibitor-bound alpha-synuclein oligomers is obviously required for the better understanding of the inhibitory mechanism. In order to characterize inhibitor-bound alpha-synucleins in detail, we have prepared alpha-synuclein dimers in the presence of polyphenol inhibitors, exifone, gossypetin, and dopamine, and purified the products. Peptide mapping and mass spectrometric analysis revealed that exifone-treated alpha-synuclein monomer and dimer were oxidized at all four methionine residues of alpha-synuclein. Immunoblot analysis and redox-cycling staining of endoproteinase Asp-N-digested products showed that the N-terminal region (1-60) is involved in the dimerization and exifone binding of alpha-synuclein. Ultra-high-field NMR analysis of inhibitor-bound alpha-synuclein dimers showed that the signals derived from the N-terminal region of alpha-synuclein exhibited line broadening, confirming that the N-terminal region is involved in inhibitor-induced dimerization. The C-terminal portion still predominantly exhibited the random-coil character observed in monomeric alpha-synuclein. We propose that the N-terminal region of alpha-synuclein plays a key role in the formation of alpha-synuclein assemblies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
395
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
445-56
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Characterization of inhibitor-bound alpha-synuclein dimer: role of alpha-synuclein N-terminal region in dimerization and inhibitor binding.
pubmed:affiliation
Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. yyoshiki@riken.jp
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't