1nrv
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| , resolution 1.65Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | GRB10 OR GRBIR OR KIAA0207 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the SH2 domain of Grb10
OverviewOverview
Grb7, Grb10, and Grb14 are members of a distinct family of adapter proteins that interact with various receptor tyrosine kinases upon receptor activation. Proteins in this family contain several modular signaling domains including a pleckstrin homology (PH) domain, a BPS (between PH and SH2) domain, and a C-terminal Src homology 2 (SH2) domain. Although SH2 domains are typically monomeric, we show that the Grb10 SH2 domain and also full-length Grb10 gamma are dimeric in solution under physiologic conditions. The crystal structure of the Grb10 SH2 domain at 1.65-A resolution reveals a non-covalent dimer whose interface comprises residues within and flanking the C-terminal alpha helix, which are conserved in the Grb7/Grb10/Grb14 family but not in other SH2 domains. Val-522 in the BG loop (BG3) and Asp-500 in the EF loop (EF1) are positioned to interfere with the binding of the P+3 residue of a phosphopeptide ligand. These structural features of the Grb10 SH2 domain will favor binding of dimeric, turn-containing phosphotyrosine sequences, such as the phosphorylated activation loops in the two beta subunits of the insulin and insulin-like growth factor-1 receptors. Moreover, the structure suggests the mechanism by which the Grb7 SH2 domain binds selectively to pTyr-1139 (pYVNQ) in Her2, which along with Grb7 is co-amplified in human breast cancers.
About this StructureAbout this Structure
1NRV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity., Stein EG, Ghirlando R, Hubbard SR, J Biol Chem. 2003 Apr 11;278(15):13257-64. Epub 2003 Jan 27. PMID:12551896
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