Adoption of a turn conformation drives the binding affinity of p53 C-terminal domain peptides to 14-3-3σ

Ave Kuusk, Joaõ Filipe Neves, Kenny Bravo-Rodriguez, Anders Gunnarsson, Yasser B. Ruiz-Blanco, Michael Ehrmann, Hongming Chen, Isabelle Landrieu (Corresponding author), Elsa Sanchez-Garcia (Corresponding author), Helen Boyd (Corresponding author), Christian Ottmann (Corresponding author), Richard G. Doveston (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

6 Downloads (Pure)

Samenvatting

The interaction between the adapter protein 14-3-3σ and transcription factor p53 is important for preserving the tumor-suppressor functions of p53 in the cell. A phosphorylated motif within the C-terminal domain (CTD) of p53 is key for binding to the amphipathic groove of 14-3-3. This motif is unique among 14-3-3 binding partners, and the precise dynamics of the interaction is not yet fully understood. Here, we investigate this interaction at the molecular level by analyzing the binding of different length p53 CTD peptides to 14-3-3σ using ITC, SPR, NMR, and MD simulations. We observed that the propensity of the p53 peptide to adopt turn-like conformation plays an important role in the binding to the 14-3-3σ protein. Our study contributes to elucidate the molecular mechanism of the 14-3-3-p53 binding and provides useful insight into how conformation properties of a ligand influence protein binding.

Originele taal-2Engels
Pagina's (van-tot)262-271
Aantal pagina's10
TijdschriftACS Chemical Biology
Volume15
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 17 jan 2020

    Vingerafdruk

Citeer dit

Kuusk, A., Neves, J. F., Bravo-Rodriguez, K., Gunnarsson, A., Ruiz-Blanco, Y. B., Ehrmann, M., ... Doveston, R. G. (2020). Adoption of a turn conformation drives the binding affinity of p53 C-terminal domain peptides to 14-3-3σ. ACS Chemical Biology, 15(1), 262-271. https://doi.org/10.1021/acschembio.9b00893