2auh
From Proteopedia
(New page: 200px<br /> <applet load="2auh" size="450" color="white" frame="true" align="right" spinBox="true" caption="2auh, resolution 3.20Å" /> '''Crystal structure o...) |
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| - | [[Image:2auh.gif|left|200px]]<br /> | + | [[Image:2auh.gif|left|200px]]<br /><applet load="2auh" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2auh" size=" | + | |
caption="2auh, resolution 3.20Å" /> | caption="2auh, resolution 3.20Å" /> | ||
'''Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase'''<br /> | '''Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AUH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | + | 2AUH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AUH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Daly, R | + | [[Category: Daly, R J.]] |
| - | [[Category: Depetris, R | + | [[Category: Depetris, R S.]] |
[[Category: Gimpelevich, I.]] | [[Category: Gimpelevich, I.]] | ||
| - | [[Category: Holt, L | + | [[Category: Holt, L J.]] |
[[Category: Hu, J.]] | [[Category: Hu, J.]] | ||
| - | [[Category: Hubbard, S | + | [[Category: Hubbard, S R.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: bps region]] | [[Category: bps region]] | ||
[[Category: yrosine kinase]] | [[Category: yrosine kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:31:09 2008'' |
Revision as of 14:31, 21 February 2008
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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 diseases 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 with as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 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
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