Deuteron Quadrupolar Chemical Exchange Saturation Transfer (Q-CEST) Solid-State NMR for Static Powder Samples: Approach and Applications to Amyloid-? Fibrils.

ABSTRACT: We provide an experimental and computational framework for ² H quadrupolar chemical exchange saturation transfer NMR experiments (Q-CEST) under static solid-state conditions for the quantification of dynamics on ?s-ms timescales. Simulations using simple 2-site exchange models provide insights into the relation between spin dynamics and motions. Biological applications focus on two sites of amyloid-? fibrils in the 3-fold symmetric polymorph. The first site, the methyl group of A2 of the disordered N-terminal domain, undergoes diffusive motions and conformational exchange due to transient interactions. Earlier ² H rotating frame relaxation and quadrupolar CPMG measurements are combined with the Q-CEST approach to characterize the multiple conformational states of the domain. The second site, the methyl group of M35, spans the water-accessible cavity inside the fibrils' core and undergoes extensive rotameric exchange. Q-CEST permits us to refine the rotameric exchange model for this site and allows the more precise determination of populations and rotameric exchange rate constants than line shape analysis.

SUBMITTER: Vugmeyster L 

PROVIDER: S-EPMC7002291 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature