2AUH

Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase

Summary for 2AUH

• Entry DOI: 10.2210/pdb2auh/pdb
• Descriptor: Insulin receptor, Growth factor receptor-bound protein 14, CALCIUM ION (3 entities in total)
• Functional Keywords: tyrosine kinase, bps region, transferase-signaling protein complex, transferase/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P06213; Cytoplasm: Q14449
• Total number of polymer chains: 2
• Total formula weight: 41439.91

Authors

Depetris, R.S.,Hu, J.,Gimpelevich, I.,Holt, L.J.,Daly, R.J.,Hubbard, S.R. (deposition date: 2005-08-27, release date: 2005-11-01, Last modification date: 2024-11-20)

Primary citation

Depetris, R.S.,Hu, J.,Gimpelevich, I.,Holt, L.J.,Daly, R.J.,Hubbard, S.R.
Structural basis for inhibition of the insulin receptor by the adaptor protein grb14.
Mol.Cell, 20:325-333, 2005

PubMed Abstract: 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.

PubMed: 16246733
DOI: 10.1016/j.molcel.2005.09.001

Experimental method

X-RAY DIFFRACTION (3.2 Å)