3bu3
From Proteopedia
(New page: 200px<br /><applet load="3bu3" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bu3, resolution 1.65Å" /> '''Crystal structure of...) |
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caption="3bu3, resolution 1.65Å" /> | caption="3bu3, resolution 1.65Å" /> | ||
'''Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide'''<br /> | '''Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide'''<br /> | ||
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| + | ==Overview== | ||
| + | Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2. | ||
==About this Structure== | ==About this Structure== | ||
3BU3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BU3 OCA]. | 3BU3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BU3 OCA]. | ||
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| + | ==Reference== | ||
| + | Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2., Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR, Nat Struct Mol Biol. 2008 Mar;15(3):251-8. Epub 2008 Feb 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18278056 18278056] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: carbohydrate metabolism]] | [[Category: carbohydrate metabolism]] | ||
| - | [[Category: cleavage on pair of basic | + | [[Category: cleavage on pair of basic residue]] |
[[Category: diabetes mellitus]] | [[Category: diabetes mellitus]] | ||
[[Category: disease mutation]] | [[Category: disease mutation]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Mar 14 09:44:10 2008'' |
Revision as of 07:44, 14 March 2008
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Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide
Overview
Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2.
About this Structure
3BU3 is a Protein complex structure of sequences from Homo sapiens. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
Reference
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2., Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR, Nat Struct Mol Biol. 2008 Mar;15(3):251-8. Epub 2008 Feb 17. PMID:18278056
Page seeded by OCA on Fri Mar 14 09:44:10 2008
Categories: Homo sapiens | Protein complex | Receptor protein-tyrosine kinase | Hubbard, S R. | Wu, J. | Alternative splicing | Atp-binding | Carbohydrate metabolism | Cleavage on pair of basic residue | Diabetes mellitus | Disease mutation | Glycoprotein | Insulin receptor | Irk | Irs2 | Kinase | Krlb | Membrane | Nucleotide-binding | Peptide | Phosphoprotein | Polymorphism | Substrate | Transducer | Transferase | Transmembrane | Tyrosine-protein kinase
