Deuteron Solid-State NMR Relaxation Measurements Reveal Two Distinct Conformational Exchange Processes in the Disordered N-Terminal Domain of Amyloid-β Fibrils
| Autor: | Liliya Vugmeyster, Dan Fai Au, Riqiang Fu, Dmitry Ostrovsky |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Amyloid
Materials science Protein Conformation 010402 general chemistry 01 natural sciences Article 03 medical and health sciences Protein Domains Bound state Side chain Tensor Physical and Theoretical Chemistry Diffusion (business) Nuclear Magnetic Resonance Biomolecular 030304 developmental biology 0303 health sciences Amyloid beta-Peptides Isotropy Relaxation (NMR) Deuterium Atomic and Molecular Physics and Optics Peptide Fragments 0104 chemical sciences Solid-state nuclear magnetic resonance Chemical physics |
| Zdroj: | Chemphyschem |
| ISSN: | 1439-7641 |
| Popis: | We employed deuterium solid-state NMR techniques under static conditions to discern the details of the μs-ms timescale motions in the flexible N-terminal subdomain of Aβ(1-40) amyloid fibrils, which spans residues 1–16. In particular, we utilized a rotating frame (R(1ρ)) and the newly developed time domain quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) relaxation measurements at the selectively deuterated side chains of A2, H6, and G9. The two experiments are complementary in terms of probing somewhat different timescales of motions, governed by the tensor parameters and the sampling window of the magnetization decay curves. The results indicated two mobile “free” states of the N-terminal domain undergoing global diffusive motions, with isotropic diffusion coefficients of 0.7–1·10(8) and 0.3–3·10(6) rad(2)/s. The free states are also involved in the conformational exchange with a single bound state, in which the diffusive motions are quenched, likely due to transient interactions with the structured hydrophobic core. The conformational exchange rate constants are 2–3·10(5) s(−1) and 2–3·10(4) s(−1) for the fast and slow diffusion free states, respectively. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text