4WC8

Heterogeneous dodecamer formed from macrocycles containing a sequence from beta-2-microglobulin(63-69).

4WC8 の概要

• エントリーDOI: 10.2210/pdb4wc8/pdb
• 分子名称: ORN-TYR-LEU-LEU-PHI-TYR-THR-GLU-ORN-LYS-VAL-ALA-MAA-ALA-VAL-LYS, ORN-TYR-LEU-LEU-PHI-TYR-THR-GLU-ORN-LYS-VAL-ALA-MLE-ALA-VAL-LYS, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: heterogeneous dodecamer, hexamer, dimers, immune system
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 25654.05

構造登録者

Spencer, R.K.,Nowick, J.S. (登録日: 2014-09-04, 公開日: 2015-05-06, 最終更新日: 2023-12-27)

主引用文献

Spencer, R.K.,Kreutzer, A.G.,Salveson, P.J.,Li, H.,Nowick, J.S.
X-ray Crystallographic Structures of Oligomers of Peptides Derived from beta 2-Microglobulin.
J.Am.Chem.Soc., 137:6304-6311, 2015

PubMed Abstract: Amyloid diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes share common features of toxic soluble protein oligomers. There are no structures at atomic resolution of oligomers formed by full-length amyloidogenic peptides and proteins, and only a few structures of oligomers formed by peptide fragments. The paucity of structural information provides a fundamental roadblock to understanding the pathology of amyloid diseases and developing preventions or therapies. Here, we present the X-ray crystallographic structures of three families of oligomers formed by macrocyclic peptides containing a heptapeptide sequence derived from the amyloidogenic E chain of β2-microglobulin (β2m). Each macrocyclic peptide contains the heptapeptide sequence β2m63-69 and a second heptapeptide sequence containing an N-methyl amino acid. These peptides form β-sheets that further associate into hexamers, octamers, and dodecamers: the hexamers are trimers of dimers; the octamers are tetramers of dimers; and the dodecamers contain two trimer subunits surrounded by three pairs of β-sheets. These structures illustrate a common theme in which dimer and trimer subunits further associate to form a hydrophobic core. The seven X-ray crystallographic structures not only illustrate a range of oligomers that a single amyloidogenic peptide sequence can form, but also how mutation can alter the size and topology of the oligomers. A cocrystallization experiment in which a dodecamer-forming peptide recruits a hexamer-forming peptide to form mixed dodecamers demonstrates that one species can dictate the oligomerization of another. These findings should also be relevant to the formation of oligomers of full-length peptides and proteins in amyloid diseases.

PubMed: 25915729
DOI: 10.1021/jacs.5b01673

実験手法

X-RAY DIFFRACTION (1.908 Å)