Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
Verlagsversion
Forschungsdaten
DOI
PMC
 |
Open Access Gold |
|
möglich sobald bei der ZB eingereicht worden ist.
Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains.
Sci. Rep. 7:41515 (2017)
Verlagsversion
Forschungsdaten
DOI
PMC
Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution-and solid-state NMR studies as well as MD simulations to characterise the interaction of EGCG with LC variable domains. We identified two distinct EGCG binding sites, both of which include a proline as an important recognition element. The binding sites were confirmed by site-directed mutagenesis and solid-state NMR analysis. The EGCG-induced protein complexes are unstructured. We propose a general mechanistic model for EGCG binding to a conserved site in LCs. We find that EGCG reacts selectively with amyloidogenic mutants. This makes this compound a promising lead structure, that can handle the immense sequence variability of antibody LCs.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Primary Systemic Amyloidosis; V-l Domain; Green Tea; Al Amyloidosis; Thermal-stability; Crystal-structure; Variable Domains; Nmr-spectroscopy; Fibril Formation; Constant-region
ISSN (print) / ISBN
2045-2322
e-ISSN
2045-2322
Zeitschrift
Scientific Reports
Quellenangaben
Band: 7,
Artikelnummer: 41515
Verlag
Nature Publishing Group
Verlagsort
London
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Structural Biology (STB)