Role of the region 23-28 in Abeta fibril formation: insights from simulations of the monomers and dimers of Alzheimer's peptides Abeta40 and Abeta42 |
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Authors: | Melquiond Adrien Dong Xiao Mousseau Normand Derreumaux Philippe |
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Affiliation: | Laboratoire de Biochimie Théorique, UPR9080 CNRS, Institut de Biologie Physico-Chimique et Université Paris 7 Denis-Diderot, Paris, France. |
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Abstract: | Self-assembly of the 40/42 amino acid Abeta peptide is a key player in Alzheimer's disease. Abeta40 is the most prevalent species, while Abeta42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of Abeta monomer and a bent in this region could be the rate-limiting step in Abeta fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of Abeta(21-30) and the monomers Abeta40 and Abeta42. On the basis of new simulations on dimers of full-length Abeta, we propose that the rate-limiting step involves the formation of a multimeric beta-sheet spanning the central hydrophobic core (residues 17-21). |
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