6IC3

AL amyloid fibril from a lambda 1 light chain

6IC3 の概要

• エントリーDOI: 10.2210/pdb6ic3/pdb
• EMDBエントリー: 4452
• 分子名称: lambda 1 light chain fragment, residues 3-118 (1 entity in total)
• 機能のキーワード: amyloid fibril, beta sheet, antibody, heart, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 97419.70

構造登録者

Fritz, G.,Faendrich, M.,Schmidt, M.,Radamaker, L. (登録日: 2018-12-02, 公開日: 2019-04-03, 最終更新日: 2019-12-18)

主引用文献

Radamaker, L.,Lin, Y.H.,Annamalai, K.,Huhn, S.,Hegenbart, U.,Schonland, S.O.,Fritz, G.,Schmidt, M.,Fandrich, M.
Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis.
Nat Commun, 10:1103-1103, 2019

PubMed Abstract: Amyloid fibrils derived from antibody light chains are key pathogenic agents in systemic AL amyloidosis. They can be deposited in multiple organs but cardiac amyloid is the major risk factor of mortality. Here we report the structure of a λ1 AL amyloid fibril from an explanted human heart at a resolution of 3.3 Å which we determined using cryo-electron microscopy. The fibril core consists of a 91-residue segment presenting an all-beta fold with ten mutagenic changes compared to the germ line. The conformation differs substantially from natively folded light chains: a rotational switch around the intramolecular disulphide bond being the crucial structural rearrangement underlying fibril formation. Our structure provides insight into the mechanism of protein misfolding and the role of patient-specific mutations in pathogenicity.

PubMed: 30894526
DOI: 10.1038/s41467-019-09032-0

実験手法

ELECTRON MICROSCOPY (3.3 Å)