3TKZ: Structure Of The Shp-2 N-Sh2 Domain In A 1:2 Complex With Rvipyfvplnr Peptide

Src homology 2 (SH2) domains mediate protein-protein interactions by recognizing phosphotyrosine (pY)-containing sequences of target proteins. In all of the SH2 domain-pY peptide interactions described to date, the SH2 domain binds to a single pY peptide. Here, determination of the cocrystal structure of the N-terminal SH2 domain of phosphatase SHP-2 bound to a class IV peptide (VIpYFVP) revealed a noncanonical 1:2 (protein-peptide) complex. The first peptide binds in a canonical manner with its pY side chain inserted in the usual binding pocket, while the second pairs up with the first to form two antiparallel beta-strands that extend the central beta-sheet of the SH2 domain. This unprecedented binding mode was confirmed in the solution phase by NMR experiments and shown to be adopted by pY peptides derived from cellular proteins. Site-directed mutagenesis and surface plasmon resonance studies revealed that the binding of the first peptide is pY-dependent, but phosphorylation is not required for the second peptide. Our findings suggest a potential new function for the SH2 domain as a molecular clamp to promote dimerization of signaling proteins.
PDB ID: 3TKZDownload
MMDB ID: 94671
PDB Deposition Date: 2011/8/29
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3TKZ: trimeric; determined by author and by software (PISA)
Molecular Components in 3TKZ
Label Count Molecule
Proteins (3 molecules)
Tyrosine-protein Phosphatase Non-receptor Type 11(Gene symbol: PTPN11)
Molecule annotation
Protein (Rvipyfvplnr Peptide)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB