Hidden motions and motion-induced invisibility: Dynamics-based spectral editing in solid-state NMR

Area of Science:

• Biophysics
• Structural Biology
• Biochemistry

Background:

• Solid-state nuclear magnetic resonance (ssNMR) spectroscopy is vital for characterizing complex biological assemblies like protein aggregates and viral capsids.
• Molecular dynamics within these biological samples significantly influence ssNMR experiment outcomes, presenting both opportunities and challenges.
• High mobility in certain protein regions can cause signal loss, complicating structural analysis using traditional ssNMR.

Purpose of the Study:

• To leverage the inherent sensitivity of ssNMR to molecular dynamics for enhanced structural characterization.
• To develop and apply novel ssNMR techniques that overcome limitations imposed by protein motion.
• To enable the detailed study of substructures within dynamic biological assemblies.

Main Methods:

• Implementation of dynamics-based spectral editing (DYSE) ssNMR techniques.
• Exploiting motion-dependent signal attenuation to differentiate between distinct motional properties within a sample.
• Applying these methods to various biological assemblies, including amyloid fibrils and membrane proteins.

Main Results:

• DYSE methods effectively simplify complex ssNMR spectra by selectively reducing signals from highly dynamic regions.
• This spectral simplification allows for the detailed investigation of less dynamic or conformationally distinct substructures.
• Successful application to diverse biological systems, demonstrating the versatility and power of DYSE-ssNMR.

Conclusions:

• Dynamics-based spectral editing (DYSE) is a powerful approach to overcome challenges posed by molecular dynamics in ssNMR.
• DYSE-ssNMR enables the structural and dynamic characterization of biological assemblies previously inaccessible due to motion-induced signal loss.
• This methodology significantly advances the capability of ssNMR for studying complex biological systems.