期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41467-019-09133-w
关键词
-
资金
- University of Milano
- Fondazione Romeo and Enrica Invernizzi
- Fondazione Cariplo [2015-0591, 2016-0489]
- Associazione Italiana per la Ricerca sul Cancro special program 5 per mille [9965]
- Italian Ministry of Health [RF-2013-02355259, RF-2016-02361756]
- Italian Medicines Agency [AIFA-2016-02364602]
- E-Rare JTC 2016 grant ReDox
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 angstrom 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 angstrom stacking and cross-beta architecture. Two distinct polypeptide stretches (total of 77 residues) from the LC variable domain (V-l) fit the fibril density. Despite Vl high sequence variability, residues stabilizing the fibril core are conserved through different cardiotoxic V-l, 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据