Inhibition of Light Chain 6aJL2-R24G Amyloid Fiber Formation Associated with Light Chain Amyloidosis

Light chain amyloidosis (AL) is a deadly disease characterized by the deposition of monoclonal immunoglobulin light chains as insoluble amyloid fibrils in different organs and tissues. Germ line λ VI has been closely related to this condition; moreover, the R24G mutation is present in 25% of the pro...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Easton) 2015-08, Vol.54 (32), p.4978-4986
Main Authors: Pelaez-Aguilar, Angel E, Rivillas-Acevedo, Lina, French-Pacheco, Leidys, Valdes-Garcia, Gilberto, Maya-Martinez, Roberto, Pastor, Nina, Amero, Carlos
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
Amyloid - antagonists & inhibitors
Amyloid - biosynthesis
Amyloid - genetics
Amyloidosis - drug therapy
Amyloidosis - genetics
Amyloidosis - metabolism
Catechin - analogs & derivatives
Catechin - pharmacology
Humans
Immunoglobulin Light Chains - biosynthesis
Immunoglobulin Light Chains - drug effects
Immunoglobulin Light Chains - genetics
In Vitro Techniques
Melatonin - pharmacology
Microscopy, Electron, Transmission
Models, Molecular
Molecular Sequence Data
Mutation, Missense
Nuclear Magnetic Resonance, Biomolecular
Protein Binding - drug effects
Protein Multimerization - drug effects
Quercetin - pharmacology
Recombinant Proteins - biosynthesis
Recombinant Proteins - drug effects
Recombinant Proteins - genetics
Rifampin - pharmacology
Tetracycline - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Light chain amyloidosis (AL) is a deadly disease characterized by the deposition of monoclonal immunoglobulin light chains as insoluble amyloid fibrils in different organs and tissues. Germ line λ VI has been closely related to this condition; moreover, the R24G mutation is present in 25% of the proteins of this germ line in AL patients. In this work, five small molecules were tested as inhibitors of the formation of amyloid fibrils from the 6aJL2-R24G protein. We have found by thioflavin T fluorescence and transmission electron microscopy that EGCG inhibits 6aJL2-R24G fibrillogenesis. Furthermore, using nuclear magnetic resonance spectroscopy, dynamic light scattering, and isothermal titration calorimetry, we have determined that the inhibition is due to binding to the protein in its native state, interacting mainly with aromatic residues.
ISSN:0006-2960
1520-4995
DOI:10.1021/acs.biochem.5b00288