Publication details
Detailed insight into dynamics of intrinsically disordered proteins using high-resolution relaxometry
| Authors | |
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| Year of publication | 2023 |
| Type | Appeared in Conference without Proceedings |
| MU Faculty or unit | |
| Citation | |
| Description | Dynamics are known to be very important for proteins allowing them to fulfill their function in the living organisms as was documented by multiple examples of globular proteins. The dynamics and conformational plasticity appear to be even more critical for intrinsically disordered proteins (IDPs), allowing them to adopt various conformations, to bind multiple ligand targets, and to play their typical roles in signaling pathways and regulations of cellular molecular machinery. Nuclear magnetic resonance (NMR) was recognized to be a unique experimental method capable of providing a detailed description of dynamics of biomolecules with atomic resolution at various timescales. The internal dynamics in the range of picoseconds and nanoseconds is most typical for IDPs and can be studied by analysing NMR relaxation rates. However, such studies are usually limited by the number of magnetic fields at which the relaxation rates can be collected. Especially the relaxation rates at low magnetic fields (below 9.4 T) are often not accessible for biomolecules because a higher magnetic field is required to reach a sufficient resolution and sensitivity necessary for studies of biomolecules including IDPs. Unfortunately, the data at low magnetic fields holds a majority of information about motions slower than a few nanoseconds related to important segmental motions of IDPs. High-resolution relaxometry was suggested to overcome this problem. The sample is transferred very rapidly between positions of the stray field with different magnetic fields and the high-field magnetic center, granting a possibility to detect at high magnetic fields necessary for high resolution and sensitivity, and to record relaxation rates at a low magnetic field within a single NMR experiment. Here, we present two case studies where such an approach has been successfully applied to IDPs. First, the delta subunit of RNA polymerase from Bacillus subtilis represents a challenging system of a protein containing both structured and disordered domain. Its disordered domain contains a highly repetitive sequence which makes the analysis very challenging, yet the analysis provides a detailed insight into its dynamics. Second, we studied the internal dynamics of osteopontin and we described the effects of heparin binding to osteopontin on its internal motions. |
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