8GJD

X-ray crystallographic structure of a beta-hairpin peptide derived from Abeta 17-36. (ORN)LVFFAED(ORN)AII(N-Me-Gly)LMV

これはPDB形式変換不可エントリーです。

8GJD の概要

• エントリーDOI: 10.2210/pdb8gjd/pdb
• 分子名称: Beta-hairpin peptide derived from Abeta 17-36, IODIDE ION (3 entities in total)
• 機能のキーワード: oligomer, trimer, amyloid, alzheimer's disease, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 30894.02

構造登録者

Kreutzer, A.G.,Ruttenberg, S.M.,Nowick, J.S.,Truex, N.L. (登録日: 2023-03-15, 公開日: 2024-01-17, 最終更新日: 2024-01-31)

主引用文献

Ruttenberg, S.M.,Kreutzer, A.G.,Truex, N.L.,Nowick, J.S.
beta-Hairpin Alignment Alters Oligomer Formation in A beta-Derived Peptides.
Biochemistry, 63:212-218, 2024

PubMed Abstract: Amyloid-β (Aβ) forms heterogeneous oligomers, which are implicated in the pathogenesis of Alzheimer's disease (AD). Many Aβ oligomers consist of β-hairpin building blocks─Aβ peptides in β-hairpin conformations. β-Hairpins of Aβ can adopt a variety of alignments, but the role that β-hairpin alignment plays in the formation and heterogeneity of Aβ oligomers is poorly understood. To explore the effect of β-hairpin alignment on the oligomerization of Aβ peptides, we designed and studied two model peptides with two different β-hairpin alignments. Peptides Aβm and Aβm mimic two different β-hairpins that Aβ can form, the Aβ and Aβ β-hairpins, respectively. These hairpins are similar in composition but differ in hairpin alignment, altering the facial arrangements of the side chains of the residues that they contain. X-ray crystallography and SDS-PAGE demonstrate that the difference in facial arrangement between these peptides leads to distinct oligomer formation. In the crystal state, Aβm forms triangular trimers that further assemble to form hexamers, while Aβm forms tetrameric β-barrels. In SDS-PAGE, Aβm assembles to form a ladder of oligomers, while Aβm either assembles to form a dimer or does not assemble at all. The differences in the behavior of Aβm and Aβm suggest β-hairpin alignment as a source of the observed heterogeneity of Aβ oligomers.

PubMed: 38163326
DOI: 10.1021/acs.biochem.3c00526

実験手法

X-RAY DIFFRACTION (2.03 Å)