1o9u
From Proteopedia
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==Overview== | ==Overview== | ||
Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase, involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation, and destruction. We have now determined the crystal structure of GSK3beta, in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A, resolution. The structure confirms the co-localization of the binding, sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals, significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta., Detailed comparison of the axin and FRAT GSK3beta complexes allows the, generation of highly specific mutations, which abrogate binding of one or, the other. Quantitative analysis suggests that the interaction of GSK3beta, with the axin scaffold enhances phosphorylation of beta-catenin by >20, 000-fold. | Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase, involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation, and destruction. We have now determined the crystal structure of GSK3beta, in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A, resolution. The structure confirms the co-localization of the binding, sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals, significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta., Detailed comparison of the axin and FRAT GSK3beta complexes allows the, generation of highly specific mutations, which abrogate binding of one or, the other. Quantitative analysis suggests that the interaction of GSK3beta, with the axin scaffold enhances phosphorylation of beta-catenin by >20, 000-fold. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Caudal duplication anomaly OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603816 603816]], Hepatocellular carcinoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603816 603816]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:31:03 2007'' |
Revision as of 16:24, 12 November 2007
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GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH AXIN PEPTIDE
Contents |
Overview
Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase, involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation, and destruction. We have now determined the crystal structure of GSK3beta, in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A, resolution. The structure confirms the co-localization of the binding, sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals, significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta., Detailed comparison of the axin and FRAT GSK3beta complexes allows the, generation of highly specific mutations, which abrogate binding of one or, the other. Quantitative analysis suggests that the interaction of GSK3beta, with the axin scaffold enhances phosphorylation of beta-catenin by >20, 000-fold.
Disease
Known diseases associated with this structure: Caudal duplication anomaly OMIM:[603816], Hepatocellular carcinoma, somatic OMIM:[603816]
About this Structure
1O9U is a Protein complex structure of sequences from Homo sapiens with ADZ as ligand. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex., Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH, EMBO J. 2003 Feb 3;22(3):494-501. PMID:12554650
Page seeded by OCA on Mon Nov 12 18:31:03 2007
Categories: Homo sapiens | Protein complex | Transferred entry: 2.7.11.1 | Dajani, R. | Pearl, L.H. | Roe, S.M. | ADZ | Anti-oncogene | Apoptosis | Developmental protein | Insulin pathway | Kinase | Multigene family | Phosphorylation | Phosphorylation; alternative splicing | Serine/threonine -protein kinase; atp-binding | Transferase
