Spatial structure of beta-amyloid Aβ1-40 in complex with a biological membrane model

The spatial structure of beta-amyloid Aβ1-40 in complex with sodium dodecyl sulfate micelles as a model membrane system was investigated by 1 H-1 H two-dimensional NMR (TOCSY, NOESY) spectroscopy and molecular dynamic method calculations. On the basis of NOE and chemical shifts changes data, spatial structure of the complex beta-amyloid-model of the cell surface membrane was obtained. Keywords: NMR; 1 H NMR; Two-Dimensional NMR (TOCSY, NOESY) Spectroscopy; Alzheimer’s Disease; Beta-Amyloid; Oligopeptides; Micelle 1. INTRODUCTION Alzheimer’s disease (AD) is a neurodegenerative sickness, which is characterized by the presence of amyloid plaques and neurofibrillar tangles in brain tissue. Products of enzymatic cleavage of a precursor peptide, amyloid precursor protein (APP) [1] are small peptides, 39 - 43 amino acid residues in length, called amyloid Aβpeptides. APP is a 695 - 770 residue transmembrane protein which is found in all mammals. When APP is cleaved sequentially by α-, β-, and γ-secretases Aβ-peptides are produced. Among amyloid-β peptides, the most abundant Aβ1-40 species is the 40-amino-acid-long version (Figure 1), but several of the highly aggregationprone Aβ1-42 and Aβ1-43 are also present in amyloid plaques of AD patients. There is increasing proofs that prefibrillar intermediates and/or the fibrils themselves play a significant role in neurodegeneration [2-7]. To discover medicines to prevent the development of AD, it may be necessary to understand the exact mechanism of amyloid Aβ-peptide aggregation. Interaction of amyloid peptides with the cellular membrane believed to be is one of the mechanisms for the neurotoxicity of amyloid peptides [8,9]. Therefore, structural studies on Aβ1-40 

The spatial structure of beta-amyloid Aβ1-40 in complex with sodium dodecyl sulfate micelles as a model membrane system was investigated by 1 H-1 H two-dimensional NMR (TOCSY, NOESY) spectroscopy and molecular dynamic method calculations. On the basis of NOE and chemical shifts changes data, spatial structure of the complex beta-amyloid-model of the cell surface membrane was obtained. Keywords: NMR; 1 H NMR; Two-Dimensional NMR (TOCSY, NOESY) Spectroscopy; Alzheimer’s Disease; Beta-Amyloid; Oligopeptides; Micelle 1. INTRODUCTION Alzheimer’s disease (AD) is a neurodegenerative sickness, which is characterized by the presence of amyloid plaques and neurofibrillar tangles in brain tissue. Products of enzymatic cleavage of a precursor peptide, amyloid precursor protein (APP) [1] are small peptides, 39 - 43 amino acid residues in length, called amyloid Aβpeptides. APP is a 695 - 770 residue transmembrane protein which is found in all mammals. When APP is cleaved sequentially by α-, β-, and γ-secretases Aβ-peptides are produced. Among amyloid-β peptides, the most abundant Aβ1-40 species is the 40-amino-acid-long version (Figure 1), but several of the highly aggregationprone Aβ1-42 and Aβ1-43 are also present in amyloid plaques of AD patients. There is increasing proofs that prefibrillar intermediates and/or the fibrils themselves play a significant role in neurodegeneration [2-7]. To discover medicines to prevent the development of AD, it may be necessary to understand the exact mechanism of amyloid Aβ-peptide aggregation. Interaction of amyloid peptides with the cellular membrane believed to be is one of the mechanisms for the neurotoxicity of amyloid peptides [8,9]. Therefore, structural studies on Aβ1-40