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Deuteron Solid‐State NMR Relaxation Measurements Reveal Two Distinct Conformational Exchange Processes in the Disordered N‐Terminal Domain of Amyloid‐β Fibrils
Author(s) -
Vugmeyster Liliya,
Au Dan Fai,
Ostrovsky Dmitry,
Fu Riqiang
Publication year - 2019
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201900363
Subject(s) - chemistry , relaxation (psychology) , solid state nuclear magnetic resonance , hydrogen–deuterium exchange , crystallography , diffusion , deuterium , chemical physics , nuclear magnetic resonance , thermodynamics , physics , atomic physics , psychology , social psychology , organic chemistry , hydrogen
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 ad 2 s −1 . 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.