Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 262-271 |
| Number of pages | 10 |
| Journal | ACS Chemical Biology |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 17 Jan 2020 |
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Adoption of a turn conformation drives the binding affinity of p53 C-terminal domain peptides to 14-3-3σ. / Kuusk, Ave; Neves, Joaõ Filipe; Bravo-Rodriguez, Kenny; Gunnarsson, Anders; Ruiz-Blanco, Yasser B.; Ehrmann, Michael; Chen, Hongming; Landrieu, Isabelle (Corresponding author); Sanchez-Garcia, Elsa (Corresponding author); Boyd, Helen (Corresponding author); Ottmann, Christian (Corresponding author); Doveston, Richard G. (Corresponding author).
In: ACS Chemical Biology, Vol. 15, No. 1, 17.01.2020, p. 262-271.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Adoption of a turn conformation drives the binding affinity of p53 C-terminal domain peptides to 14-3-3σ
AU - Kuusk, Ave
AU - Neves, Joaõ Filipe
AU - Bravo-Rodriguez, Kenny
AU - Gunnarsson, Anders
AU - Ruiz-Blanco, Yasser B.
AU - Ehrmann, Michael
AU - Chen, Hongming
AU - Landrieu, Isabelle
AU - Sanchez-Garcia, Elsa
AU - Boyd, Helen
AU - Ottmann, Christian
AU - Doveston, Richard G.
PY - 2020/1/17
Y1 - 2020/1/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85078512786&partnerID=8YFLogxK
U2 - 10.1021/acschembio.9b00893
DO - 10.1021/acschembio.9b00893
M3 - Article
C2 - 31742997
AN - SCOPUS:85078512786
VL - 15
SP - 262
EP - 271
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8937
IS - 1
ER -