Abstract
Many details pertaining to the formation and interactions of protein aggregates associated with neurodegenerative diseases are invisible to conventional biophysical techniques. We recently introduced (15)N dark-state exchange saturation transfer (DEST) and (15)N lifetime line-broadening to study solution backbone dynamics and position-specific binding probabilities for amyloid β (Aβ) monomers in exchange with large (2-80 MDa) protofibrillar Aβ aggregates. Here we use (13)C(methyl)DEST and lifetime line-broadening to probe the interactions and dynamics of methyl-bearing side chains in the Aβ-protofibril-bound state. We show that all methyl groups of Aβ40 populate direct-contact bound states with a very fast effective transverse relaxation rate, indicative of side-chain-mediated direct binding to the protofibril surface. The data are consistent with position-specific enhancements of (13)C(methyl)-R₂(tethered) values in tethered states, providing further insights into the structural ensemble of the protofibril-bound state.
Original language | English (US) |
---|---|
Pages (from-to) | 10345-10349 |
Number of pages | 5 |
Journal | Angewandte Chemie (International ed. in English) |
Volume | 53 |
Issue number | 39 |
DOIs | |
State | Published - Sep 22 2014 |
Externally published | Yes |
Keywords
- NMR spectroscopy
- amyloid β
- high-molecular-weight assemblies
- protein-protein interactions
ASJC Scopus subject areas
- General Chemistry
- Catalysis