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Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of alpha-synuclein, a molecular chaperone

Authors
 Sang Myun Park  ;  Han Young Jung  ;  Thomas D. Kim  ;  Jeon Han Park  ;  Chul Hak Yang  ;  Jongsun Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.277(32) : 28512-28520, 2002 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2002
MeSH
Animals ; Chromatography, Gel ; Cloning, Molecular ; Escherichia coli/metabolism ; Genetic Vectors ; Glutathione Transferase/metabolism ; Humans ; Mutagenesis, Site-Directed ; Nerve Tissue Proteins/chemistry* ; Peptides/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Substrate Specificity ; Synucleins ; Temperature ; Tetrahydrofolate Dehydrogenase/chemistry ; Time Factors ; alpha-Synuclein
Abstract
α-Synuclein, an acidic neuronal protein of 140 amino acids, is extremely heat-resistant and is natively unfolded. Recent studies have demonstrated that α-synuclein has chaperone activity both in vitro and in vivo, and that this activity is lost upon removing its C-terminal acidic tail. However, the detailed mechanism of the chaperone action of α-synuclein remains unknown. In this study, we investigated the molecular mechanism of the chaperone action of α-synuclein by analyzing the roles of its N-terminal and C-terminal domains. The N-terminal domain (residues 1–95) was found to bind to substrate proteins to form high molecular weight complexes, whereas the C-terminal acidic tail (residues 96–140) appears to be primarily involved in solubilizing the high molecular weight complexes. Because the substrate-binding domain and the solubilizing domain for chaperone function are well separated in α-synuclein, the N-terminal-binding domain can be substituted by other proteins or peptides. Interestingly, the resultant engineered chaperone proteins appeared to display differential efficiency and specificity in terms of the chaperone function, which depended upon the nature of the binding domain. This finding implies that the C-terminal acidic tail of α-synuclein can be fused with other proteins or peptides to engineer synthetic chaperones for specific purposes.
Files in This Item:
T200205691.pdf Download
DOI
10.1074/jbc.M111971200
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
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143868
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