5SUR

X-ray crystallographic structure of a covalent trimer derived from A-beta 17_36. Synchrotron data set. (ORN)CVF(MEA)CED(ORN)AIIGL(ORN)V.

5SUR の概要

• エントリーDOI: 10.2210/pdb5sur/pdb
• 関連するPDBエントリー: 5SUS 5SUT 5SUU
• 分子名称: 16mer A-beta peptide: ORN-CYS-VAL-PHE-MEA-CYS-GLU-ASP-ORN-ALA-ILE-ILE-GLY-LEU-ORN-VAL, SODIUM ION, HEXANE-1,6-DIOL, ... (5 entities in total)
• 機能のキーワード: amyloid, oligomer, alzheimer's, trimer, protein fibril, de novo protein
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 7730.30

構造登録者

Kreutzer, A.G.,Yoo, S.,Nowick, J.S. (登録日: 2016-08-03, 公開日: 2017-01-11, 最終更新日: 2024-03-27)

主引用文献

Kreutzer, A.G.,Yoo, S.,Spencer, R.K.,Nowick, J.S.
Stabilization, Assembly, and Toxicity of Trimers Derived from A beta.
J.Am.Chem.Soc., 139:966-975, 2017

PubMed Abstract: Oligomers of the β-amyloid peptide Aβ have emerged as important contributors to neurodegeneration in Alzheimer's disease. Mounting evidence suggests that Aβ trimers and higher-order oligomers derived from trimers have special significance in the early stages of Alzheimer's disease. Elucidating the structures of these trimers and higher-order oligomers is paramount for understanding their role in neurodegeneration. This paper describes the design, synthesis, X-ray crystallographic structures, and biophysical and biological properties of two stabilized trimers derived from the central and C-terminal regions of Aβ. These triangular trimers are stabilized through three disulfide cross-links between the monomer subunits. The X-ray crystallographic structures reveal that the stabilized trimers assemble hierarchically to form hexamers, dodecamers, and annular porelike structures. Solution-phase biophysical studies reveal that the stabilized trimers assemble in solution to form oligomers that recapitulate some of the higher-order assemblies observed crystallographically. The stabilized trimers share many of the biological characteristics of oligomers of full-length Aβ, including toxicity toward a neuronally derived human cell line, activation of caspase-3 mediated apoptosis, and reactivity with the oligomer-specific antibody A11. These studies support the biological significance of the triangular trimer assembly of Aβ β-hairpins and may offer a deeper understanding of the molecular basis of Alzheimer's disease.

PubMed: 28001392
DOI: 10.1021/jacs.6b11748

実験手法

X-RAY DIFFRACTION (1.801 Å)