PDBsum entry 4jmh

De novo protein

PDB id: 4jmh

Contents

Protein chain

200 a.a.

Ligands

HIS-GLN-PTR-PTR-ASN-ASP-PHE-PRO

Waters ×7

PDB id:

4jmh

Name:

De novo protein

Title:

Crystal structure of synthetic protein in complex with double py peptide

Structure:

Clamp shc1_py239/240. Chain: a. Engineered: yes. Shc-transforming protein 1. Chain: b. Fragment: unp residues 344-356. Synonym: shc-transforming protein 3, shc-transforming protein a, src homology 2 domain-containing-transforming protein c1, sh2 domain protein c1.

Source:

Synthetic construct. Organism_taxid: 32630. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: shc, shc1, shca. Expression_system_taxid: 562

Resolution:

2.41Å R-factor: 0.216 R-free: 0.276

Authors:

N.Yasui,L.Smith,S.Koide

Key ref:

N.Yasui et al. (2014). Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation. Mol Cell, 54, 1034-1041. PubMed id: 24910098 DOI: 10.1016/j.molcel.2014.05.002

Date:

14-Mar-13 Release date: 23-Apr-14

Protein chain

No UniProt id for this chain

Struc: 200 a.a.

DOI no: 10.1016/j.molcel.2014.05.002

Mol Cell 54:1034-1041 (2014)

PubMed id: 24910098

Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation.

N.Yasui, G.M.Findlay, G.D.Gish, M.S.Hsiung, J.Huang, M.Tucholska, L.Taylor, L.Smith, W.C.Boldridge, A.Koide, T.Pawson, S.Koide.

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.