Intrinsically disordered proteins (IDPs), i.e. proteins without stable three-dimensional structure, are extremely dynamic and it is precisely this dynamics that allows them to function and bind to different interaction partners very easily and efficiently. Rather than describing IDPs with a single structure, ensembles of many conformers have to be calculated to adequately represent their conformational landscape. In the past, nuclear magnetic resonance (NMR) spectroscopy and small angle X-ray scattering (SAXS) have been used to provide experimental input for the calculation of such ensembles. A precise description of specific long-range distances has, however, so-far been missing.
IBS/FDP researchers (Naudi-Fabra et al.) have now combined single molecule fluorescence spectroscopy, Förster resonance energy transfer (FRET) in particular, providing precise distances up to 10 nanometers, with NMR spectroscopy and SAXS in order to determine conformational ensembles in agreement with all those experimental data. The authors could show that their calculated ensembles were of predictive nature and reproduced independent data that were not included in the calculation of the model. This multidisciplinary approach thus opens up new possibilities for the quantitative description of intrinsically disordered proteins.
Quantitative description of Intrinsically Disordered Proteins using single molecule FRET, NMR and SAXS. Naudi-Fabra S, Tengo M, Jensen MR, Blackledge M, Milles S. J Am Chem Soc In Press (2021) https://doi.org/10.1021/jacs.1c06264
Contact : Sigrid Milles (Protein Dynamics and Flexibility by NMR Group)