High-Affinity Binding of Monomeric but Not Oligomeric Amyloid-β to Ganglioside GM1 Containing Nanodiscs
| Autor: | Lothar Gremer, Philipp Neudecker, Dieter Willbold, Christina Dammers, Judith Fabig, Maren Thomaier |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Magnetic Resonance Spectroscopy Lipid Bilayers Kinetics Cell G(M1) Ganglioside Plasma protein binding Binding Competitive Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease medicine Animals Humans Polyacrylamide gel electrophoresis Phospholipids Amyloid beta-Peptides Ganglioside Cell Membrane Nuclear magnetic resonance spectroscopy Peptide Fragments Nanostructures 030104 developmental biology Monomer Membrane medicine.anatomical_structure chemistry Electrophoresis Polyacrylamide Gel lipids (amino acids peptides and proteins) Protein Multimerization 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Biochemistry. 55:6662-6672 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/acs.biochem.6b00829 |
| Popis: | The interaction of the amyloid-β protein (Aβ) with neuronal cell membranes plays a crucial role in Alzheimer's disease. Aβ undergoes structural changes upon binding to ganglioside GM1 containing membranes leading to altered molecular characteristics of the protein. The physiological role of the Aβ interaction with the ganglioside GM1 is still unclear. In order to further elucidate the molecular requirements of Aβ membrane binding, we tested different nanodiscs varying in their lipid composition, regarding the charge of the headgroups as well as ganglioside GM1 concentration. Nanodiscs are excellent model membrane systems for studying protein membrane interactions, and we show here their suitability to investigate the membrane interaction of Aβ. In particular, we set out to investigate whether the binding activity of GM1 to Aβ is specific for the assembly state of Aβ and compared the binding affinities of monomeric with oligomeric Aβ. Using fluorescence titration experiments, we demonstrate high-affinity binding of Aβ(1-40) to GM1 containing nanodiscs, with dissociation constants, K |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|