 |
PDBsum entry 2auh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/signaling protein
|
PDB id
|
|
|
|
2auh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for inhibition of the insulin receptor by the adaptor protein grb14.
|
|
|
Authors
|
|
R.S.Depetris,
J.Hu,
I.Gimpelevich,
L.J.Holt,
R.J.Daly,
S.R.Hubbard.
|
|
|
Ref.
|
|
Mol Cell, 2005,
20,
325-333.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1. Crystal Structure of the Grb14(BPS)-IRK Complex
|
|
Figure 4.
Figure 4. Model for the Interaction of Grb14 with the
Insulin Receptor
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
20,
325-333)
copyright 2005.
|
|
|
|
|
|
|
