3Q9J

AIIFL segment derived from Alzheimer's Amyloid-Beta displayed on 42-membered macrocycle scaffold

3Q9J の概要

• エントリーDOI: 10.2210/pdb3q9j/pdb
• 関連するPDBエントリー: 3Q9G 3Q9H 3Q9I
• 分子名称: Cyclic pseudo-peptide AIIFL(ORN)(HAO)YK(ORN), ZINC ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: beta sheet tetramer, macrocyclic peptide, beta-sheet mimic, amyloid-like oligomer, protein fibril
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 11594.01

構造登録者

Liu, C.,Sawaya, M.R.,Eisenberg, D.,Nowick, J.S.,Cheng, P.,Zheng, J. (登録日: 2011-01-07, 公開日: 2011-06-08, 最終更新日: 2023-11-15)

主引用文献

Liu, C.,Sawaya, M.R.,Cheng, P.N.,Zheng, J.,Nowick, J.S.,Eisenberg, D.
Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic beta-Sheet Mimics.
J.Am.Chem.Soc., 133:6736-6744, 2011

PubMed Abstract: Protein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. β-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from Aβ and tau were incorporated into macrocycles, thereby restraining them to β-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which β-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a variety of sheet-to-sheet pairing angles, offering a structural explanation for the heterogeneity of amyloid oligomers.

PubMed: 21473620
DOI: 10.1021/ja200222n

実験手法

X-RAY DIFFRACTION (2.55 Å)