1O9U: Glycogen Synthase Kinase 3 Beta Complexed With Axin Peptide

Citation:
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.
PDB ID: 1O9UDownload
MMDB ID: 24125
PDB Deposition Date: 2002/12/19
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 1O9U: tetrameric; determined by author and by software (PQS)
Molecular Components in 1O9U
Label Count Molecule
Proteins (4 molecules)
2
Glycogen Synthase Kinase-3 Beta(Gene symbol: GSK3B)
Molecule annotation
2
Axin Peptide(Gene symbol: AXIN1)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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