4JMH

Crystal structure of synthetic protein in complex with double pY peptide

Summary for 4JMH

• Entry DOI: 10.2210/pdb4jmh/pdb
• Related: 4JMG
• Descriptor: Clamp Shc1_pY239/240, SHC-transforming protein 1 (3 entities in total)
• Functional Keywords: synthetic protein, binding to double py containing sequence, de novo protein
• Biological source: synthetic construct; More
• Cellular location: Cytoplasm. Isoform p46Shc: Mitochondrion matrix. Isoform p66Shc: Mitochondrion (By similarity): P29353
• Total number of polymer chains: 2
• Total formula weight: 24073.54

Authors

Yasui, N.,Smith, L.,Koide, S. (deposition date: 2013-03-14, release date: 2014-04-23, Last modification date: 2024-11-20)

Primary citation

Yasui, N.,Findlay, G.M.,Gish, G.D.,Hsiung, M.S.,Huang, J.,Tucholska, M.,Taylor, L.,Smith, L.,Boldridge, W.C.,Koide, A.,Pawson, T.,Koide, S.
Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation.
Mol.Cell, 54:1034-1041, 2014

PubMed Abstract: 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.

PubMed: 24910098
DOI: 10.1016/j.molcel.2014.05.002

Experimental method

X-RAY DIFFRACTION (2.408 Å)