Adoption of a Turn Conformation Drives the Binding Affinity of p53 C-Terminal Domain Peptides to 14-3-3σ | Zendy

Ave Kuusk | Zendy; João Filipe Neves | Zendy; Kenny BravoRodriguez | Zendy; Anders Gunnarsson | Zendy; Yasser B. RuizBlanco | Zendy; Michael Ehrmann | Zendy; Hongming Chen | Zendy; Isabelle Landrieu | Zendy; Elsa SánchezGarcía | Zendy; Helen Boyd | Zendy; Christian Ottmann | Zendy; Richard G. Doveston | Zendy

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Adoption of a Turn Conformation Drives the Binding Affinity of p53 C-Terminal Domain Peptides to 14-3-3σ

Author(s) -

Ave Kuusk,

João Filipe Neves,

Kenny BravoRodriguez,

Anders Gunnarsson,

Yasser B. RuizBlanco,

Michael Ehrmann,

Hongming Chen,

Isabelle Landrieu,

Elsa SánchezGarcía,

Helen Boyd,

Christian Ottmann,

Richard G. Doveston

Publication year - 2019

Publication title -

acs chemical biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.899

H-Index - 111

eISSN - 1554-8937

pISSN - 1554-8929

DOI - 10.1021/acschembio.9b00893

Subject(s) - peptide , binding site , c terminus , plasma protein binding , turn (biochemistry) , biophysics , transcription factor , molecular dynamics , chemistry , stereochemistry , protein–protein interaction , binding selectivity , computational biology , biochemistry , biology , amino acid , gene , computational chemistry

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.

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