Hydrogen Exchange-Mass Spectrometry Analysis of β-Amyloid Peptide Structure
Resource
Biochemistry 42 (31): 9507-9514
Journal
Biochemistry
Journal Volume
42
Journal Issue
31
Pages
9507-9514
Date Issued
2003
Date
2003
Author(s)
Abstract
beta-Amyloid peptide (A beta) is the primary protein component of senile plaques in Alzheimer's disease and is believed to be responsible for the neurodegeneration associated with the disease. A beta has proven to be toxic only when aggregated; however, the structure of the aggregated species associated with toxicity is unknown. In the present study, we use hydrogen-deuterium isotope exchange (HX)-electrospray ionization mass spectrometry (MS) along with enzymatic digestion as a tool to examine at near residue level, the changes in A beta structure associated with aggregation to a fibril form. Our results show that the structure of A beta intermediate species formed early in the course of fibrillogenesis is dependent upon solvent conditions. Additionally, the HX-MS data of peptic A beta fragments suggest that the C-terminal segment of the peptide is approximately 35% protected from exchange in fibril-containing samples, relative to monomeric A beta species prepared in DMSO/H(2)O. The N-terminus (residues 1-4) is completely unprotected from exchange, and the fragment containing residues 5-19 is over 50% protected from exchange in the fibril-containing samples. This work contributes to our understanding of A beta structure associated with aggregation and toxicity and further application of this approach may aid in the design of agents that intervene in the A beta aggregation processes associated with neurotoxicity.
Other Subjects
Agglomeration; Disease control; Ion exchange; Ionization; Mass spectrometry; Toxicity; Hydrogen exchange; Proteins; amyloid beta protein; deuterium; dimethyl sulfoxide; hydrogen; peptide fragment; solvent; water; Alzheimer disease; amino terminal sequence; article; carboxy terminal sequence; fibrillogenesis; fibrogenesis; hydrogen exchange mass spectrometry; mass spectrometry; nerve degeneration; priority journal; protein aggregation; protein degradation; protein structure; senile plaque; structure analysis; Amyloid beta-Protein; Congo Red; Fluorescence; Humans; Hydrogen; Hydrophobicity; Peptide Fragments; Protein Structure, Tertiary; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thiazoles
Type
journal article
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