Dihedral Angle Measurements for Structure Determination by Biomolecular Solid-State NMR Spectroscopy

Abstract

In structural studies of immobilized, aggregated and self-assembled biomolecules, solid-state NMR (ssNMR) spectroscopy can provide valuable high-resolution structural information. Among the structural restraints provided by magic angle spinning (MAS) ssNMR the canonical focus is on inter-atomic distance measurements. In the current review, we examine the utility of ssNMR measurements of angular constraints, as a complement to distance-based structure determination. The focus is on direct measurements of angular restraints via the judicious recoupling of multiple anisotropic ssNMR parameters, such as dipolar couplings and chemical shift anisotropies. Recent applications are highlighted, with a focus on studies of nanocrystalline polypeptides, aggregated peptides and proteins, receptor-substrate interactions, and small molecule interactions with amyloid protein fibrils. The review also examines considerations of when and where ssNMR torsion angle experiments are (most) effective, and discusses challenges and opportunities for future applications.

Solid-state nuclear magnetic resonance in the structural study of polyglutamine aggregation

“…Does this mean that ssNMR structure determination is not feasible in polyQ amyloid? Previous structural studies of amyloidogenic polypeptides [ 44–46 ] deployed measurements of another structural parameter: torsion angles [ 47 ]. Specialized ssNMR experiments allow the determination of the relative orientations of neighboring chemical bonds (e.g.…”

“…This allows one to constrain the backbone (Ramachandran angles) and side-chain torsion angles (rotamer states). For a more in-depth discussion of these experiments, readers are referred to a recent review article [ 47 ]. In polyQ amyloids, these experiments were applied to backbone and side-chain dihedral angles of glutamine residues within the amyloid core ( Figure 2E,F ) [ 25 , 28 ].…”

“…Both conformations reflect β-sheet structure, but they differ in their Ramachandran angles ( Figure 2E ) and rotamer states ( Figure 2F ). These findings were based on the application of so-called NCCN and HCCH dihedral angle measurements, where dipolar interactions were recoupled between carbons, nitrogens and protons [ 28 , 47 ]. Antiparallel β-sheets are inherently expected (and observed) to assemble by alternating β-strands with different backbone conformations ( Figure 2C ; red/blue arrows) [ 48 ].…”

The Structure of Boron Monoxide

“…Multidimensional NMR experiments enable the correlation of two anisotropic quantities and the determination of the relative orientations between moieties. 27 This is extensively used in biomolecular solid-state NMR where dipole−dipole, 28−31 dipole−CSA, 32−35 and CSA− CSA 36,37 correlation experiments are used to determine backbone torsion angles. 3-coordinate boron is well known to have an electric field gradient (EFG) tensor that is oriented along the moiety's plane normally.…”

“…For instance, the chemical shift tensor of an aromatic carbon is positioned with its smallest component oriented along the ring’s normal vector, while the dipolar coupling tensor is oriented along the internuclear axis. Multidimensional NMR experiments enable the correlation of two anisotropic quantities and the determination of the relative orientations between moieties . This is extensively used in biomolecular solid-state NMR where dipole–dipole, − dipole–CSA, − and CSA–CSA , correlation experiments are used to determine backbone torsion angles.…”