3P1S

Crystal structure of human 14-3-3 sigma C38N/N166H in complex with TASK-3 peptide and stabilizer fusicoccin A

Summary for 3P1S

• Entry DOI: 10.2210/pdb3p1s/pdb
• Related: 2O98 3IQV 3M50 3P1N 3P1O 3P1P 3P1Q 3P1R
• Descriptor: 14-3-3 protein sigma, 6-mer peptide from Potassium channel subfamily K member 9, FUSICOCCIN, ... (6 entities in total)
• Functional Keywords: helical protein, phosphoprotein, adapter protein, peptide binding protein, nucleus
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P31947; Cell membrane ; Multi-pass membrane protein : Q9NPC2
• Total number of polymer chains: 2
• Total formula weight: 28184.78

Authors

Anders, C.,Higuchi, Y.,Schumacher, B.,Thiel, P.,Kato, N.,Ottmann, C. (deposition date: 2010-09-30, release date: 2011-10-12, Last modification date: 2024-10-30)

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 (1.65 Å)