2F8O

A Native to Amyloidogenic Transition Regulated by a Backbone Trigger

2F8O の概要

• エントリーDOI: 10.2210/pdb2f8o/pdb
• 分子名称: Beta-2-microglobulin (2 entities in total)
• 機能のキーワード: beta-sandwich, amyloid, class-1 mhc, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted . Note=(Microbial infection) In the presence of M: P61769
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23706.64

構造登録者

Eakin, C.M.,Berman, A.J.,Miranker, A.D. (登録日: 2005-12-02, 公開日: 2006-02-21, 最終更新日: 2024-11-20)

主引用文献

Eakin, C.M.,Berman, A.J.,Miranker, A.D.
A native to amyloidogenic transition regulated by a backbone trigger.
Nat.Struct.Mol.Biol., 13:202-208, 2006

PubMed Abstract: Many polypeptides can self-associate into linear, aggregated assemblies termed amyloid fibers. High-resolution structural insights into the mechanism of fibrillogenesis are elusive owing to the transient and mixed oligomeric nature of assembly intermediates. Here, we report the conformational changes that initiate fiber formation by beta-2-microglobulin (beta2m) in dialysis-related amyloidosis. Access of beta2m to amyloidogenic conformations is catalyzed by selective binding of divalent cations. The chemical basis of this process was determined to be backbone isomerization of a conserved proline. On the basis of this finding, we designed a beta2m variant that closely adopts this intermediate state. The variant has kinetic, thermodynamic and catalytic properties consistent with its being a fibrillogenic intermediate of wild-type beta2m. Furthermore, it is stable and folded, enabling us to unambiguously determine the initiating conformational changes for amyloid assembly at atomic resolution.

PubMed: 16491088
DOI: 10.1038/nsmb1068

実験手法

X-RAY DIFFRACTION (1.7 Å)