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Aluminum-Induced Structural Alterations of the Precursorof the Non-AbComponent of Alzheimer’s Disease Amyloid

Authors
 Seung R. Paik  ;  Ju-Hyun Lee  ;  Do-Hyung Kim  ;  Chung-Soon Chang  ;  Jongsun Kim 
Citation
 ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, Vol.344(2) : 325-334, 1997 
Journal Title
 ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 
ISSN
 0003-9861 
Issue Date
1997
MeSH
Aluminum/pharmacology* ; Alzheimer Disease/metabolism* ; Amino Acid Sequence ; Amyloid/chemistry* ; Amyloid/genetics ; Amyloid/metabolism ; Calpain/metabolism ; Chymotrypsin/metabolism ; Circular Dichroism ; Electrophoresis, Polyacrylamide Gel ; Humans ; Molecular Sequence Data ; Molecular Weight ; Nerve Tissue Proteins* ; Neurofibrillary Tangles/metabolism ; Protein Conformation/drug effects* ; Protein Precursors/chemistry* ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Sequence Analysis ; Spectrometry, Fluorescence ; Spectrophotometry ; Synucleins ; Trypsin/metabolism
Abstract
The precursor of the non-A beta component of Alzheimer's disease amyloid (NACP) is a presynaptic protein whose function has been suspected to be tightly involved in neuronal biogenesis including synaptic regulations. NACP was suggested to seed the neuritic plaque formation in the presence of A beta during the development of Alzheimer's disease (AD). Recombinant NACP purified through heat treatment, DEAE-Sephacel anion-exchange, Sephacryl S-200 size-exclusion, and S-Sepharose cation-exchange chromatography steps appeared as a single band on SDS-PAGE with Mr of 19 kDa. Its N-terminal amino acid sequence clearly confirmed that the protein was NACP. Interestingly, however, the protein was split into a doublet on a nondenaturing (ND)-PAGE with equal intensities. The doublet was located slightly above a 45-kDa marker protein on a 12.5% ND-PAGE. In addition, the size of NACP was more carefully estimated as 53 kDa with high-performance gel-permeation chromatography using a TSK G3000sw size-exclusion column. Recently, Lansbury and his colleagues (Biochemistry 35, 13709-13715) have reported that NACP exists as an elongated "natively unfolded" structure which would make the protein more actively involved in protein-protein interactions and Kim (Mol. Cells 7, 78-83) has also shown that the natively unfolded protein is extremely sensitive to proteases. Here, we report that the structure of NACP could be altered by certain environmental factors. Aluminum, a suspected risk factor for AD, converged the doublet of NACP into a singlet with slightly lower mobility on ND-PAGE. Spectroscopic analysis employing uv absorption, intrinsic fluorescence, and circular dichroism indicated that NACP experienced the structural alterations in the presence of aluminum such as the secondary structure transition to generate about 33% alpha-helix. This altered structure of NACP became resistant to proteases such as trypsin, alpha-chymotrypsin, and calpain. Therefore, it is suggested that aluminum, which influences two pathologically critical processes in AD such as the protein turnover and the protein aggregation via the structural modifications, could participate in the disease.
Full Text
https://www.sciencedirect.com/science/article/pii/S0003986197902071?via%3Dihub
DOI
10.1006/abbi.1997.0207
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/22282913/177260
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