Nuclear Magnetic Resonance (NMR) Spectroscopy is a unique tool to study complex systems such as biological macromolecules due to its ability to probe molecular structure and dynamics at atomic resolution and on a wide range of timescales. During the last decades major progresses have been made towards the description of biomolecular dynamics and protein folding. However, fundamental questions remain open.
Chaperone proteins are key elements in regulating protein folding and aggregation prevention. Despite their critical biological role, the mechanisms by which chaperone proteins interact with their substrates remain quite elusive, in part due to the major role played by conformational disorder.
To investigate this question and more generally propose a strategy to study transient biomolecular interactions between flexible partners, we developed an approach combining NMR spectroscopy and corse grain modeling, where the information obtained on the two partners is used to implement a system specific force-field encoding the accessible experimental knowledge on that system.
With this approach we depicted the interaction between Spy, a recently discovered chaperone, and Im7, an in vivo substrate. The approach provided us a detailed picture at the residue level of a chaperone-substrate interaction allowing for a detailed description of the role of conformational disorder in chaperone action. The results were in agreement with multiple other experimental information including from x-ray crystallography, attesting the robustness of the method.
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Salmon et al. Meth. Mol. Biol., vol 1764 (2018)