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Structural changes in alpha-synuclein affect its chaperone-like activity in vitro

Authors
 Thomas D. Kim  ;  Seung R. Paik  ;  Chul-Hak Yang  ;  Jongsun Kim 
Citation
 Protein Science, Vol.9(12) : 2489-2496, 2000 
Journal Title
PROTEIN SCIENCE
ISSN
 0961-8368 
Issue Date
2000
MeSH
Albumins/drug effects ; Dimerization ; Dithiothreitol/pharmacology ; Enzymes/drug effects ; Enzymes/metabolism ; Humans ; Molecular Chaperones* ; Nerve Tissue Proteins/chemistry* ; Nerve Tissue Proteins/drug effects ; Nerve Tissue Proteins/pharmacology* ; Parkinson Disease/etiology ; Protein Denaturation/drug effects ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Recombinant Proteins/drug effects ; Recombinant Proteins/pharmacology ; Structure-Activity Relationship ; Synucleins ; Temperature ; Zinc/pharmacology ; alpha-Synuclein
Keywords
a-synuclein ; molecular chaperone ; Parkinson’s disease ; protein folding ; structural change
Abstract
Alpha-synuclein, a major constituent of Lewy bodies (LBs) in Parkinson's disease (PD), has been implicated to play a critical role in synaptic events, such as neuronal plasticity during development, learning, and degeneration under pathological conditions, although the physiological function of alpha-synuclein has not yet been established. We here present biochemical evidence that recombinant alpha-synuclein has a chaperone-like function against thermal and chemical stress in vitro. In our experiments, alpha-synuclein protected glutathione S-transferase (GST) and aldolase from heat-induced precipitation, and alpha-lactalbumin and bovine serum albumin from dithiothreitol (DTT)-induced precipitation like other molecular chaperones. Moreover, preheating of alpha-synuclein, which is believed to reorganize the molecular surface of alpha-synuclein, increased the chaperone-like activity. Interestingly, in organic solvents, which promotes the formation of secondary structure, alpha-synuclein aggregated more easily than in its native condition, which eventually might abrogate the chaperone-like function of the protein. In addition, alpha-synuclein was also rapidly and significantly precipitated by heat in the presence of Zn2+ in vitro, whereas it was not affected by the presence of Ca2+ or Mg2+. Circular dichroism spectra confirmed that alpha-synuclein underwent conformational change in the presence of Zn2+. Taken together, our data suggest that alpha-synuclein could act as a molecular chaperone, and that the conformational change of the alpha-synuclein could explain the aggregation kinetics of alpha-synuclein, which may be related to the abolishment of the chaperonic-like activity.
Files in This Item:
T200001595.pdf Download
DOI
10.1110/ps.9.12.2489
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171846
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