Format

Send to

Choose Destination
J Biol Chem. 2012 Mar 16;287(12):9081-9. doi: 10.1074/jbc.M111.292086. Epub 2012 Jan 25.

Solid-support electron paramagnetic resonance (EPR) studies of Aβ40 monomers reveal a structured state with three ordered segments.

Author information

1
Department of Neurology, Brain Research Institute, Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.

Abstract

Alzheimer disease is associated with the pathological accumulation of amyloid-β peptide (Aβ) in the brain. Soluble Aβ oligomers formed during early aggregation process are believed to be neurotoxins and causative agents in Alzheimer disease. Aβ monomer is the building block for amyloid assemblies. A comprehensive understanding of the structural features of Aβ monomer is crucial for delineating the mechanism of Aβ oligomerization. Here we investigated the structures of Aβ40 monomer using a solid-support approach, in which Aβ40 monomers are tethered on the solid support via an N-terminal His tag to prevent further aggregation. EPR spectra of tethered Aβ40 with spin labels at 18 different positions show that Aβ40 monomers adopt a completely disordered structure under denaturing conditions. Under native conditions, however, EPR spectra suggest that Aβ40 monomers adopt both a disordered state and a structured state. The structured state of Aβ40 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 Aβ aggregation.

PMID:
22277652
PMCID:
PMC3308762
DOI:
10.1074/jbc.M111.292086
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center