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bioRxiv · 10.1101/2021.06.10.447870

The dynamic properties of a nuclear coactivator binding domain are evolutionarily conserved

Karlsson, E.·Sorgenfrei, F. A.·Andersson, E.·Dogan, J.·Jemth, P.·chi, c.
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Abstract

Evolution of proteins is constrained by their structure and function. While there is a consensus that the plasticity of intrinsically disordered proteins relaxes the structural constraints on evolution there is a paucity of data on the molecular details of these processes. The Nuclear co-activator binding domain (NCBD) from CREB-binding protein is a protein-protein interaction domain, which contains a hydrophobic core but is not behaving as a typical globular domain, and has been desribed as molten-globule like. The highly dynamic properties of NCBD makes it an interesting model system for evolutionary structure-function investigation of intrinsically disordered proteins. We have here compared the structure and biophysical properties of an ancient version of NCBD present in a bilaterian animal ancestor living around 600 million years ago with extant human NCBD. Using a combination of NMR spectroscopy, circular dichroism and kinetic methods we show that although NCBD has increased its thermodynamic stability, it has retained its dynamic biophysical properties in the ligand-free state in the evolutionary lineage leading from the last common bilaterian ancestor to humans. Our findings suggest that the dynamic properties of NCBD have been maintained by purifying selection and thus are important for its function, which includes mediating several distinct protein-protein interactions.

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Karlsson, E., Sorgenfrei, F. A., Andersson, E., Dogan, J., Jemth, P., chi, c.. 2021-06-10. The dynamic properties of a nuclear coactivator binding domain are evolutionarily conserved. https://doi.org/10.1101/2021.06.10.447870

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