6VU4

Structure of a beta-hairpin peptide mimic derived from Abeta 14-36

6VU4 の概要

• エントリーDOI: 10.2210/pdb6vu4/pdb
• 分子名称: Beta-hairpin Amyloid-beta precursor peptide mimic, IODIDE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: alzheimer's disease, neuropeptide
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4154.10

構造登録者

Wierzbicki, M.,Kreutzer, A.,Samdin, T.,Nowick, J.S. (登録日: 2020-02-14, 公開日: 2020-06-17, 最終更新日: 2023-10-11)

主引用文献

Samdin, T.D.,Wierzbicki, M.,Kreutzer, A.G.,Howitz, W.J.,Valenzuela, M.,Smith, A.,Sahrai, V.,Truex, N.L.,Klun, M.,Nowick, J.S.
Effects of N-Terminal Residues on the Assembly of Constrained beta-Hairpin Peptides Derived from A beta.
J.Am.Chem.Soc., 142:11593-11601, 2020

PubMed Abstract: This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic β-hairpin peptides derived from the central and C-terminal regions of Aβ, which bear "tails" derived from the N-terminus of Aβ. Soluble oligomers of the β-amyloid peptide, Aβ, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of Aβ as a region that may initiate the formation of damaging oligomeric species. We previously studied, in our laboratory, macrocyclic β-hairpin peptides derived from Aβ and Aβ, capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length Aβ, we use an orthogonal protecting group strategy during the synthesis to append residues from Aβ to the parent macrocyclic β-hairpin peptide , which comprises Aβ and Aβ. The N-terminally extended peptides , , , , , , , and assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of Aβ oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of Aβ accommodated by the oligomers as an unstructured tail.

PubMed: 32501687
DOI: 10.1021/jacs.0c05186

実験手法

X-RAY DIFFRACTION (2.077 Å)