1O9U

GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH AXIN PEPTIDE

Summary for 1O9U

• Entry DOI: 10.2210/pdb1o9u/pdb
• Related: 1DK8 1EMU 1GNG 1H8F 1I09 1O6K 1O6L
• Descriptor: GLYCOGEN SYNTHASE KINASE-3 BETA, AXIN PEPTIDE, 9-METHYL-9H-PURIN-6-AMINE, ... (4 entities in total)
• Functional Keywords: transferase-transferase substrate complex, kinase, insulin pathway, transferase, serine/threonine-protein kinase, atp-binding, multigene family, phosphorylation, developmental protein, anti-oncogene, apoptosis, transferase- transferase substrate complex, transferase/transferase substrate
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 41911.06

Authors

Dajani, R.,Pearl, L.H.,Roe, S.M. (deposition date: 2002-12-19, release date: 2003-08-15, Last modification date: 2024-11-06)

Primary citation

Dajani, R.,Fraser, E.,Roe, S.M.,Yeo, M.,Good, V.,Thompson, V.,Dale, T.C.,Pearl, L.H.
Structural Basis for Recruitment of Glycogen Synthase Kinase 3Beta to the Axin-Apc Scaffold Complex
Embo J., 22:494-, 2003

PubMed Abstract: 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.

PubMed: 12554650
DOI: 10.1093/EMBOJ/CDG068

Experimental method

X-RAY DIFFRACTION (2.4 Å)