3smo

From Proteopedia

Revision as of 02:24, 21 November 2024 by OCA (Talk | contribs)

(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)

Crystal structure of human 14-3-3 sigma C38V/N166H in complex with TASK-3 peptide and stabilizer Fusicoccin J aglycone

Structural highlights

3smo 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

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.

A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of k(+) channels at the cell surface.,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 Chem Biol. 2013 Apr 18;20(4):583-93. doi: 10.1016/j.chembiol.2013.03.015. PMID:23601647^[1]

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

References

↑ 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. 2013 Apr 18;20(4):583-93. doi: 10.1016/j.chembiol.2013.03.015. PMID:23601647 doi:http://dx.doi.org/10.1016/j.chembiol.2013.03.015