3LOW

Crystal structure of Beta 2 Microglobulin domain-swapped dimer

3LOW の概要

• エントリーDOI: 10.2210/pdb3low/pdb
• 関連するPDBエントリー: 3LOZ
• 分子名称: Beta-2-microglobulin, GLYCEROL (3 entities in total)
• 機能のキーワード: domain-swap, beta sheet hinge region, amyloidosis, inter-molecular disulfide bond, protein fibril
• 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: 24034.99

構造登録者

Liu, C.,Eisenberg, D. (登録日: 2010-02-04, 公開日: 2010-12-08, 最終更新日: 2024-10-30)

主引用文献

Liu, C.,Sawaya, M.R.,Eisenberg, D.
Beta2-microglobulin forms three-dimensional domain-swapped amyloid fibrils with disulfide linkages.
Nat.Struct.Mol.Biol., 18:49-55, 2011

PubMed Abstract: β₂-microglobulin (β₂m) is the light chain of the type I major histocompatibility complex. It deposits as amyloid fibrils within joints during long-term hemodialysis treatment. Despite the devastating effects of dialysis-related amyloidosis, full understanding of how fibrils form from soluble β₂m remains elusive. Here we show that β₂m can oligomerize and fibrillize via three-dimensional domain swapping. Isolating a covalently bound, domain-swapped dimer from β₂m oligomers on the pathway to fibrils, we were able to determine its crystal structure. The hinge loop that connects the swapped domain to the core domain includes the fibrillizing segment LSFSKD, whose atomic structure we also determined. The LSFSKD structure reveals a class 5 steric zipper, akin to other amyloid spines. The structures of the dimer and the zipper spine fit well into an atomic model for this fibrillar form of β₂m, which assembles slowly under physiological conditions.

PubMed: 21131979
DOI: 10.1038/nsmb.1948

実験手法

X-RAY DIFFRACTION (2.3 Å)