3IQJ: Crystal Structure of human 14-3-3 sigma in Complex with Raf1 peptide (10mer)

Citation:
Abstract
The Ras-RAF-mitogen-activated protein kinase (Ras-RAF-MAPK) pathway is overactive in many cancers and in some developmental disorders. In one of those disorders, namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins. We show that these mutations impair binding of 14-3-3 proteins to C-RAF and alter its subcellular localization by promoting Ras-mediated plasma membrane recruitment of C-RAF. By presenting biophysical binding data, the 14-3-3/C-RAFpS(259) crystal structure, and cellular analyses, we indicate a mechanistic link between a well-described human developmental disorder and the impairment of a 14-3-3/target protein interaction. As a broader implication of these findings, modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway.
PDB ID: 3IQJDownload
MMDB ID: 84536
PDB Deposition Date: 2009/8/20
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.15  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 3IQJ: tetrameric; determined by author and by software (PISA)
Molecular Components in 3IQJ
Label Count Molecule
Proteins (4 molecules)
2
14-3-3 Protein Sigma(Gene symbol: SFN)
Molecule annotation
2
10-mer Peptide From RAF Proto-oncogene Serine/threonine-protein Kinase(Gene symbol: RAF1)
Molecule annotation
Chemicals (8 molecules)
1
2
2
6
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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