Inhibition of Light Chain 6aJL2-R24G Amyloid Fiber Formation Associated with Light Chain Amyloidosis
| Autor: | Nina Pastor, Carlos Amero, Gilberto Valdés-García, Leidys French-Pacheco, Lina Rivillas-Acevedo, Angel E. Pelaez-Aguilar, Roberto Maya-Martinez |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Amyloid Molecular Sequence Data Mutation Missense In Vitro Techniques Immunoglobulin light chain Biochemistry Catechin chemistry.chemical_compound Microscopy Electron Transmission Dynamic light scattering Native state medicine Humans Amino Acid Sequence Nuclear Magnetic Resonance Biomolecular Melatonin Amyloidosis Fibrillogenesis Isothermal titration calorimetry Tetracycline medicine.disease Recombinant Proteins Amino Acid Substitution chemistry Immunoglobulin Light Chains Quercetin Thioflavin Protein Multimerization Rifampin Protein Binding |
| Zdroj: | Biochemistry. 54:4978-4986 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/acs.biochem.5b00288 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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