2auh
From Proteopedia
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'''Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase''' | '''Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase''' | ||
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[[Category: Hu, J.]] | [[Category: Hu, J.]] | ||
[[Category: Hubbard, S R.]] | [[Category: Hubbard, S R.]] | ||
| - | [[Category: | + | [[Category: Bps region]] |
| - | [[Category: | + | [[Category: Yrosine kinase]] |
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 16:29, 3 May 2008
Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase
Contents |
Overview
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.
Disease
Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]
About this Structure
2AUH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 19:29:30 2008
