4FR3

Crystal structure of human 14-3-3 sigma in complex with TASK-3 peptide and stabilizer 16-O-Me-FC-H

Summary for 4FR3

• Entry DOI: 10.2210/pdb4fr3/pdb
• Related: 3P1N 3SML 3UX0
• Descriptor: 14-3-3 protein sigma, TASK-3 peptide, (4R,5R,6R,6aS,9S,9aE,10aR)-5-hydroxy-9-(methoxymethyl)-6,10a-dimethyl-3-(propan-2-yl)-1,2,4,5,6,6a,7,8,9,10a-decahydrodicyclopenta[a,d][8]annulen-4-yl alpha-D-glucopyranoside, ... (5 entities in total)
• Functional Keywords: nucleus, peptide binding protein-toxin complex, peptide binding protein/toxin
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P31947
• Total number of polymer chains: 2
• Total formula weight: 27847.01

Authors

Ottmann, C.,Anders, C.,Schumacher, B. (deposition date: 2012-06-26, release date: 2013-05-08, Last modification date: 2024-11-20)

Primary citation

Anders, C.,Higuchi, Y.,Koschinsky, K.,Bartel, M.,Schumacher, B.,Thiel, P.,Nitta, H.,Preisig-Muller, R.,Schlichthorl, G.,Renigunta, V.,Ohkanda, J.,Daut, J.,Kato, N.,Ottmann, C.
A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of k(+) channels at the cell surface.
Chem.Biol., 20:583-593, 2013

PubMed Abstract: Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction. We also tested the functional effects of FC-THF on TASK channels heterologously expressed in Xenopus oocytes. Incubation with 10 μM FC-THF was found to promote the transport of TASK channels to the cell membrane, leading to a significantly higher density of channels at the surface membrane and increased potassium current.

PubMed: 23601647
DOI: 10.1016/j.chembiol.2013.03.015

Experimental method

X-RAY DIFFRACTION (1.9 Å)