Calprotectin influences the aggregation of metal-free and metal-bound amyloid- β by direct interaction

被引:9
作者
Lee, Hyuck Jin [1 ]
Savelieff, Masha G. [2 ]
Kang, Juhye [1 ,3 ]
Brophy, Megan Brunjes [4 ]
Nakashige, Toshiki G. [4 ]
Lee, Shin Jung C. [3 ]
Nolan, Elizabeth M. [4 ]
Lim, Mi Hee [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Dept Chem, Daejeon 34141, South Korea
[2] SciGency Sci Commun, Ann Arbor, MI 48104 USA
[3] UNIST, Dept Chem, Ulsan 44919, South Korea
[4] MIT, Dept Chem, Cambridge, MA 02139 USA
基金
新加坡国家研究基金会; 美国国家科学基金会;
关键词
HUMAN SERUM-ALBUMIN; ALZHEIMERS-DISEASE; A-BETA; INFLAMMATORY S100A9; ZINC-BINDING; PEPTIDE; PROTEIN; AFFINITY; OLIGOMERS; CU(II);
D O I
10.1039/c8mt00091c
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Proteins from the S100 family perform numerous functions and may contribute to Alzheimer's disease (AD). Herein, we report the effects of S100A8/S100A9 heterooligomer calprotectin (CP) and the S100B homodimer on metal-free and metal-bound amyloid- (A; A(40) and A(42)) aggregation in vitro. Studies performed with CP-Ser [S100A8(C42S)/S100A9(C3S) oligomer] indicate that the protein influences the aggregation profile for A(40) in both the absence and presence of metal ions [i.e., Zn(ii) and Cu(ii)]. Moreover, the detection of A(40)-CP-Ser complexes by mass spectrometry suggests a direct interaction as a possible mechanism for the involvement of CP in A(40) aggregation. Although the interaction of CP-Ser with A(40) impacts A(40) aggregation in vitro, the protein does not attenuate A-induced toxicity in SH-SY5Y cells. In contrast, S100B has a slight effect on the aggregation of A. Overall, this work supports a potential association of CP with A in the absence and presence of metal ions in AD.
引用
收藏
页码:1116 / 1127
页数:12
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