4JMH: Crystal Structure Of Synthetic Protein In Complex With Double Py Peptide

Cell signaling depends on dynamic protein-protein interaction (PPI) networks, often assembled through modular domains each interacting with multiple peptide motifs. This complexity raises a conceptual challenge, namely to define whether a particular cellular response requires assembly of the complete PPI network of interest or can be driven by a specific interaction. To address this issue, we designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly biased toward a single phosphotyrosine (pY) motif among many potential pYXNX Grb2-binding sites. Surprisingly, directing Grb2 predominantly to a single pY site of the Ptpn11/Shp2 phosphatase, but not other sites tested, was sufficient for differentiation of the essential primitive endoderm lineage from embryonic stem cells. Our data suggest that discrete connections within complex PPI networks can underpin regulation of particular biological events. We propose that this directed wiring approach will be of general utility in functionally annotating specific PPIs.
PDB ID: 4JMHDownload
MMDB ID: 119872
PDB Deposition Date: 2013/3/14
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 2.41  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4JMH: dimeric; determined by author and by software (PISA)
Molecular Components in 4JMH
Label Count Molecule
Proteins (2 molecules)
Clamp Shc1_py239/240
Molecule annotation
Shc-transforming Protein 1(Gene symbol: SHC1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB