7BMC

Crystal structure of 14-3-3 sigma in complex with CIP2ApS904 peptide and stabilizing Fusicoccin A

7BMC の概要

• エントリーDOI: 10.2210/pdb7bmc/pdb
• 分子名称: 14-3-3 protein sigma, VAL-ASN-LEU-SEP-ILE, FUSICOCCIN, ... (6 entities in total)
• 機能のキーワード: protein-peptide complex, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29700.09

構造登録者

Centorrino, F.,Andlovic, B.,Ottmann, C. (登録日: 2021-01-19, 公開日: 2022-03-02, 最終更新日: 2024-10-23)

主引用文献

Brink, H.J.,van Senten, J.R.,De Vries-van Leeuwen, I.J.,da Costa Pereira, D.,Piersma, S.R.,Jimenez, C.R.,Centorrino, F.,Ottmann, C.,Siderius, M.,Smit, M.J.,de Boer, A.H.
Fusicoccin-A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C-Terminal Interaction with 14-3-3.
Acs Chem.Biol., 17:2972-2978, 2022

PubMed Abstract: The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3. We demonstrate that 14-3-3 is a new interaction partner of CIP2A. The 14-3-3/CIP2A C-terminal interaction complex can be targeted by the protein-protein interaction (PPI) stabilizer fusicoccin-A (FC-A), resulting in enhanced levels of phosphorylated Ser904. FC-A treatment of TNBC cells leads to the increased association of CIP2A with 14-3-3. We show that the composite interface between 14 and 3-3 and CIP2A's C-terminus can be targeted by the PPI stabilizer FC-A, providing a new interface that could potentially be exploited to modulate CIP2A's activity.

PubMed: 36255265
DOI: 10.1021/acschembio.2c00299

実験手法

X-RAY DIFFRACTION (2 Å)