PT  - JOURNAL ARTICLE
AU  - Elin Karlsson
AU  - Frieda A. Sorgenfrei
AU  - Eva Andersson
AU  - Jakob Dogan
AU  - Per Jemth
AU  - Celestine N. Chi
TI  - The dynamic properties of a nuclear coactivator binding domain are evolutionarily conserved
AID  - 10.1101/2021.06.10.447870
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.10.447870
4099  - http://biorxiv.org/content/early/2021/06/10/2021.06.10.447870.short
4100  - http://biorxiv.org/content/early/2021/06/10/2021.06.10.447870.full
AB  - 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 verging on being intrinsically disordered. These highly dynamic ‘borderline’ properties of NCBD makes it an interesting model system for evolutionary structure-function investigation. 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 NCBD has retained its structure and dynamic biophysical properties in the ligand-free state in the evolutionary lineage leading from the bilaterian ancestor to humans. Our findings suggest that the dynamic properties of NCBD are subject to positive selection and thus important for its function, which includes mediating several distinct protein-protein interactions.Competing Interest StatementThe authors have declared no competing interest.