3P1S: Crystal structure of human 14-3-3 sigma C38N/N166H in complex with TASK-3 peptide and stabilizer fusicoccin A

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 muM 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.
PDB ID: 3P1SDownload
MMDB ID: 94210
PDB Deposition Date: 2010/9/30
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.65  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3P1S: tetrameric; determined by author and by software (PISA)
Molecular Components in 3P1S
Label Count Molecule
Proteins (4 molecules)
14-3-3 Protein Sigma(Gene symbol: SFN)
Molecule annotation
6-mer Peptide From Potassium Channel Subfamily K Member 9(Gene symbol: KCNK9)
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB