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[摘要]：Alzheimer disease is associated with the pathological accumulation of amyloid-beta peptide (A beta) in the brain. Soluble A beta oligomers formed during early aggregation process are believed to be neurotoxins and causative agents in Alzheimer disease. A beta monomer is the building block for amyloid assemblies. A comprehensive understanding of the structural features of A beta monomer is crucial for delineating the mechanism of A beta oligomerization. Here we investigated the structures of A beta 40 monomer using a solid-support approach, in which A beta 40 monomers are tethered on the solid support via an N-terminal His tag to prevent further aggregation. EPR spectra of tethered A beta 40 with spin labels at 18 different positions show that A beta 40 monomers adopt a completely disordered structure under denaturing conditions. Under native conditions, however, EPR spectra suggest that A beta 40 monomers adopt both a disordered state and a structured state. The structured state of A beta 40 monomer has three more ordered segments at 14-18, 29-30, and 38-40. Interactions between these segments may stabilize the structured state, which likely plays an important role in A beta aggregation. |
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