Dynamics in the solid-state: perspectives for the investigation of amyloid aggregates, membrane proteins and soluble protein complexes

Progress in Nuclear Magnetic Resonance Spectroscopy

2017

In this review, we discuss the experimental static deuteron NMR techniques and computational approaches most useful for the investigation of side-chain dynamics in protein systems. Focus is placed on the interpretation of line shape and relaxation data within the framework of motional modeling. We consider both jump and diffusion models and apply them to uncover glassy behaviors, conformational exchange and dynamical transitions in proteins. Applications are chosen from globular and membrane proteins, amyloid fibrils, peptide adsorbed on surfaces and proteins specific to connective tissues.

Section: Experimental Approachesmentioning

confidence: 99%

Static solid-state 2H NMR methods in studies of protein side-chain dynamics

Progress in Nuclear Magnetic Resonance Spectroscopy

2017

“…[5][6][7][28][29][30]31,[32][33][34][35][36] Site-specific studies of the dynamics of the insoluble aggregates of Aβ are rare due to challenges in obtaining the necessary resolution and sensitivity in the solid non-crystalline state. [28,[37][38][39][40][41][42] Of note are the works of Fawzi et al, [43][44] who utilized solution NMR saturation transfer approaches to probe the binding of monomeric Aβ to the surface of protofibrils and detected several states as part of the pathways of the binding of the monomer to protofibrils.…”

Section: Introductionmentioning

confidence: 99%

Deuteron Solid‐State NMR Relaxation Measurements Reveal Two Distinct Conformational Exchange Processes in the Disordered N‐Terminal Domain of Amyloid‐β Fibrils

et al. 2019

ChemPhysChem

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 Aβ1–40 amyloid fibrils, which spans residues 1–16. In particular, we utilized a rotating frame (R1ρ) 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 ⋅ 108 and 0.3−3 ⋅ 106ad2 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 ⋅ 105 s−1 and 2−3 ⋅ 104 s−1 for the fast and slow diffusion free states, respectively.

“…Investigations of methyl dynamics in solid-state can be a useful tool for non-soluble biological systems such as amyloid fibrils. 12 In the solid state one can also explore a much wider temperature range to elucidate the mechanistic details of motions, as well as perform experiments as a function of water content to probe the effects of solvent on the dynamics. 2 …”

Section: Introductionmentioning

confidence: 99%

Comparative dynamics of methionine side-chain in FMOC-methionine and in amyloid fibrils

Chemical Physics Letters

2017

We compared the dynamics of key methionine methyl groups in the water-accessible hydrophobic cavity of amyloid fibrils and Fluorenylmethyloxycarbonyl-Methionine (FMOC-Met), which renders general hydrophobicity to the environment without the complexity of the protein. Met35 in the hydrated cavity was recently found to undergo a dynamical cross-over from the dominance of methyl rotations at low temperatures to the dominance of diffusive motion of methyl axis at high temperatures. Current results indicate that in FMOC-Met this cross-over is suppressed, similar to what was observed for the dry fibrils, indicating that hydration of the cavity is driving the onset of the dynamical transition.