The inhibitory effects of Escherichia coli maltose binding protein on β-amyloid aggregation and cytotoxicity.
The aggregation of β-amyloid (Aβ) peptide from its monomeric to its fibrillar form importantly contributes to the development of Alzheimer's disease. Here, we investigated the effects of Escherichia coli maltose binding protein (MBP), which has been previously used as a fusion protein, on Aβ42 fibrillization, in order to improve understanding of the self-assembly process and the cytotoxic mechanism of Aβ42. MBP, at a sub-stoichiometric ratio with respect to Aβ42, was found to have chaperone-like inhibitory effects on β-sheet fibril formation, due to the accumulation of Aβ42 aggregates by sequestration of active Aβ42 species as Aβ42-MBP complexes. Furthermore, MBP increased the lag time of Aβ42 polymerization, decreased the growth rate of fibril extension, and suppressed Aβ42 mediated toxicity in human neuroblastoma SH-SY5Y cells. It appears that MBP decreases the active concentration of Aβ42 by sequestering it as Aβ42-MBP complex, and that this sequestration suppresses ongoing nucleation and retards the growth rate of Aβ42 species required for fibril formation. We speculate that inhibition of the growth rate of potent Aβ42 species by MBP suppresses Aβ42-mediated toxicity in SH-SY5Y cells.
Department of Bio-Materials Engineering, Chosun University, Gwanju 501-759, Republic of Korea; Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
Md Golam
MG
Sharoar
Md
M
Shahnawaz
Md Imamul
MI
Islam
Vijay Sankar
VS
Ramasamy
Song Yub
SY
Shin
Il-Seon
IS
Park
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000378:metabolism*; D006801:Humans; D058619:Maltose-Binding Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001426:Bacterial Proteins; D058619:Maltose-Binding Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins
Alzheimer’s disease; Cytotoxicity; Fibrillogenesis; Maltose binding protein; Oligomers; β-Amyloid