2aug
Crystal structure of the Grb14 SH2 domain
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OverviewOverview
Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin, homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an, intervening stretch of approximately 45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated, that Grb14 is a tissue-specific negative regulator of insulin receptor, signaling and that inhibition is mediated by the BPS region. We have, determined the crystal structure of the Grb14 BPS region in complex with, the tyrosine kinase domain of the insulin receptor. The structure reveals, that the N-terminal portion of the BPS region binds as a pseudosubstrate, inhibitor in the substrate peptide binding groove of the kinase. Together, with the crystal structure of the SH2 domain, we present a model for the, interaction of Grb14 with the insulin receptor, which indicates how Grb14, functions as a selective protein inhibitor of insulin signaling.
About this StructureAbout this Structure
2AUG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14., Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ, Hubbard SR, Mol Cell. 2005 Oct 28;20(2):325-33. PMID:16246733
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