6HUD

Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain (AL) amyloidosis patient.

6HUD の概要

• エントリーDOI: 10.2210/pdb6hud/pdb
• EMDBエントリー: 0274
• 分子名称: Monoclonal immunoglobulin light chains (LC) (1 entity in total)
• 機能のキーワード: immunoglobulin light chains; amyloid cardiomyopathy; ex-vivo cryo-em; helical reconstruction;, protein fibril
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 73104.32

構造登録者

Paissoni, C.,Camilloni, C. (登録日: 2018-10-06, 公開日: 2019-03-27, 最終更新日: 2024-11-20)

主引用文献

Swuec, P.,Lavatelli, F.,Tasaki, M.,Paissoni, C.,Rognoni, P.,Maritan, M.,Brambilla, F.,Milani, P.,Mauri, P.,Camilloni, C.,Palladini, G.,Merlini, G.,Ricagno, S.,Bolognesi, M.
Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient.
Nat Commun, 10:1269-1269, 2019

PubMed Abstract: Systemic light chain amyloidosis (AL)  is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart involvement is the most important factor determining prognosis. Here, we report the 4.0 Å resolution cryo-electron microscopy map and molecular model of amyloid fibrils extracted from the heart of an AL amyloidosis patient with severe amyloid cardiomyopathy. The helical fibrils are composed of a single protofilament, showing typical 4.9 Å stacking and cross-β architecture. Two distinct polypeptide stretches (total of 77 residues) from the LC variable domain (V) fit the fibril density. Despite V high sequence variability, residues stabilizing the fibril core are conserved through different cardiotoxic V, highlighting structural motifs that may be common to misfolding-prone LCs. Our data shed light on the architecture of LC amyloids, correlate amino acid sequences with fibril assembly, providing the grounds for development of innovative medicines.

PubMed: 30894521
DOI: 10.1038/s41467-019-09133-w

実験手法

ELECTRON MICROSCOPY (4 Å)