7ob8

From Proteopedia

Crystal structure of 14-3-3 sigma in complex with LDB1 phosphopeptide and stabilizer Fusicoccin-A

Structural highlights

7ob8 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.

Publication Abstract from PubMed

The natural product family of the fusicoccanes (FCs) has been shown to display anti-cancer activity, especially when combined with established therapeutic agents. FCs stabilize 14-3-3 protein-protein interactions (PPIs). Here, we tested combinations of a small library of FCs with interferon alpha (IFNalpha) on different cancer cell lines and report a proteomics approach to identify the specific 14-3-3 PPIs that are induced by IFNalpha and stabilized by FCs in OVCAR-3 cells. Among the identified 14-3-3 target proteins are THEMIS2, receptor interacting protein kinase 2 (RIPK2), EIF2AK2, and several members of the LDB1 complex. Biophysical and structural biology studies confirm these 14-3-3 PPIs as physical targets of FC stabilization, and transcriptome as well as pathway analyses suggest possible explanations for the observed synergistic effect of IFNalpha/FC treatment on cancer cells. This study elucidates the polypharmacological effects of FCs in cancer cells and identifies potential targets from the vast interactome of 14-3-3s for therapeutic intervention in oncology.

IFNalpha primes cancer cells for Fusicoccin-induced cell death via 14-3-3 PPI stabilization.,Andlovic B, Heilmann G, Ninck S, Andrei SA, Centorrino F, Higuchi Y, Kato N, Brunsveld L, Arkin M, Menninger S, Choidas A, Wolf A, Klebl B, Kaschani F, Kaiser M, Eickhoff J, Ottmann C Cell Chem Biol. 2023 Jun 15;30(6):573-590.e6. doi: , 10.1016/j.chembiol.2023.04.005. Epub 2023 May 1. PMID:37130519^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Andlovic B, Heilmann G, Ninck S, Andrei SA, Centorrino F, Higuchi Y, Kato N, Brunsveld L, Arkin M, Menninger S, Choidas A, Wolf A, Klebl B, Kaschani F, Kaiser M, Eickhoff J, Ottmann C. IFNα primes cancer cells for Fusicoccin-induced cell death via 14-3-3 PPI stabilization. Cell Chem Biol. 2023 Jun 15;30(6):573-590.e6. PMID:37130519 doi:10.1016/j.chembiol.2023.04.005