A β-Hairpin-Binding Protein for Three Different Disease-Related Amyloidogenic Proteins

被引：27

作者：

Shaykhalishahi, Hamed ^{[1
]}

Mirecka, Ewa A. ^{[1
]}

Gauhar, Aziz ^{[1
]}

Gruening, Clara S. R. ^{[1
]}

Willbold, Dieter ^{[1
,3
]}

Hard, Torleif ^{[2
]}

Stoldt, Matthias ^{[1
,3
]}

Hoyer, Wolfgang ^{[1
,3
]}

机构：

[1] Univ Dusseldorf, Inst Phys Biol, D-40204 Dusseldorf, Germany

[2] Swedish Univ Agr Sci SLU, Dept Chem & Biotechnol, S-75007 Uppsala, Sweden

[3] Res Ctr Julich, Inst Struct Biochem ICS 6, D-52425 Julich, Germany

来源：

CHEMBIOCHEM | 2015年 / 16卷 / 03期

关键词：

amyloids; intrinsically disordered proteins; molecular recognition; protein aggregation; protein engineering; MECHANISM; PEPTIDES; STATE;

D O I：

10.1002/cbic.201402552

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：

Amyloidogenic proteins share a propensity to convert to the beta-structure-rich amyloid state that is associated with the progression of several protein-misfolding disorders. Here we show that a single engineered beta-hairpin-binding protein, the beta-wrapin AS10, binds monomers of three different amyloidogenic proteins, that is, amyloid-beta peptide, alpha-synuclein, and islet amyloid polypeptide, with sub-micromolar affinity. AS10 binding inhibits the aggregation and toxicity of all three proteins. The results demonstrate common conformational preferences and related binding sites in a subset of the amyloidogenic proteins. These commonalities enable the generation of multispecific monomer-binding agents.

引用

页码：411 / 414

页数：4

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