Assembly of Peptides Derived from β-Sheet Regions of β-Amyloid.
Assembly of Peptides Derived from β-Sheet Regions of β-Amyloid.
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DOI：
10.1021/jacs.6b06000
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发表时间：
2016-10-26
影响因子：
15
通讯作者：
Nowick JS
中科院分区：
文献类型：
--
作者：
Truex NL;Wang Y;Nowick JS
在阿尔茨海默病中，β-淀粉样肽（Aβ）的聚集导致与神经变性相关的寡聚体和原纤维的形成。Aβ的聚集通过肽的不同区域之间的相互作用发生。本文和随附的论文组成了Aβ两个关键区域的两部分研究：中心区域和C-末端区域。这两个区域促进聚集并在原纤维中采用β-折叠结构，并且在低聚物中也可以这样做。在本文中，我们研究了大环β折叠肽的组装，其中包含来自中心区域的残基17-23（LVFFAED）和来自C-末端区域的残基30-36（AIIGLMV）。这些肽组装形成四聚体。每个四聚体由两个氢键二聚体组成，它们通过疏水相互作用以类疏水方式组装。将单个15 N同位素标记掺入每个肽中提供了光谱探针，利用该光谱探针来阐明β-折叠组装和相互作用：1H，15 N HSQC研究促进了单体和四聚体的鉴定; 15 N编辑的NOESY研究证实了四聚体内二聚体的配对。在接下来的论文中，J. Am. Chem. Soc.2016，DOI：10.1021/jacs.6b06001，我们将扩展这些研究以阐明肽的共组装以形成异源四聚体。
In Alzheimer’s disease, aggregation of the β-amyloid peptide (Aβ) results in the formation of oligomers and fibrils that are associated with neurodegeneration. Aggregation of Aβ occurs through interactions between different regions of the peptide. This paper and the accompanying paper constitute a two-part investigation of two key regions of Aβ: the central region and the C-terminal region. These two regions promote aggregation and adopt β-sheet structure in the fibrils, and may also do so in the oligomers. In this paper, we study the assembly of macrocyclic β-sheet peptides that contain residues 17–23 (LVFFAED) from the central region and residues 30–36 (AIIGLMV) from the C-terminal region. These peptides assemble to form tetramers. Each tetramer consists of two hydrogen-bonded dimers that pack through hydrophobic interactions in a sandwich-like fashion. Incorporation of a single 15N isotopic label into each peptide provides a spectroscopic probe with which to elucidate the β-sheet assembly and interaction: 1H,15N HSQC studies facilitate the identification of the monomers and tetramers; 15N-edited NOESY studies corroborate the pairing of the dimers within the tetramers. In the following paper, J. Am. Chem. Soc.2016, DOI: 10.1021/jacs.6b06001, we will extend these studies to elucidate the coassembly of the peptides to form heterotetramers.
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影响因子：
21.8
作者：
通讯作者：
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影响因子：
15
作者：
Do TD;LaPointe NE;Nelson R;Krotee P;Hayden EY;Ulrich B;Quan S;Feinstein SC;Teplow DB;Eisenberg D;Shea JE;Bowers MT
通讯作者：
Bowers MT
影响因子：
15
作者：
Nowick, JS;Brower, JO
通讯作者：
Brower, JO
影响因子：
120.7
作者：
Näslund, J;Haroutunian, V;Buxbaum, JD
通讯作者：
Buxbaum, JD
DOI：
10.1073/pnas.0711731105
发表时间：
2008-04-01
影响因子：
11.1
作者：
Hoyer, Wolfgang;Gronwall, Caroline;Hard, Torleif
通讯作者：
Hard, Torleif