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PMID: 11707392 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex.

The EMBO journal ·Vol. 20 ·No. 22 ·2001-11-15 ·Pages 6203-12

Eklof Spink K, Fridman SG, Weis WI

Abstract

The adenomatous polyposis coli (APC) tumor suppressor protein plays a critical role in regulating cellular levels of the oncogene product beta-catenin. APC binds to beta-catenin through a series of homologous 15 and 20 amino acid repeats. We have determined the crystal structure of a 15 amino acid beta-catenin binding repeat from APC bound to the armadillo repeat region of beta-catenin. Although it lacks significant sequence homology, the N-terminal half of the repeat binds in a manner similar to portions of E-cadherin and XTcf3, but the remaining interactions are unique to APC. We discuss the implications of this new structure for the design of therapeutics, and present evidence from structural, biochemical and sequence data, which suggest that the 20 amino acid repeats can adopt two modes of binding to beta-catenin.

MeSH Terms
Adenomatous Polyposis Coli/metabolism Adenomatous Polyposis Coli Protein/metabolism Amino Acid Sequence Cadherins/chemistry Crystallography, X-Ray Cytoskeletal Proteins/chemistry,metabolism HMGB Proteins Humans Ligands Models, Molecular Molecular Sequence Data Peptides/chemistry Plasmids/metabolism Protein Binding Protein Biosynthesis Protein Structure, Tertiary Sequence Homology, Amino Acid TCF Transcription Factors Trans-Activators Transcription Factor 7-Like 1 Protein Transcription Factors/chemistry beta Catenin
Chemicals
Adenomatous Polyposis Coli Protein CTNNB1 protein, human Cadherins Cytoskeletal Proteins HMGB Proteins Ligands Peptides TCF Transcription Factors TCF7L1 protein, human Trans-Activators Transcription Factor 7-Like 1 Protein Transcription Factors beta Catenin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Eklof Spink K
Departments of Structural Biology and of Molecular and Cellular Physiology, Stanford University School of Medicine, 299 Campus Dr. West Stanford, CA 94305, USA.
Fridman S G
Weis W I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.22.6203
Published
2001-11-15
Pages
6203-12
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125720
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056169 · United States
NIGMS NIH HHS · GM56169 · United States
Databases
PDB
1JPP
External Links
PubMed source DOI: 10.1093/emboj/20.22.6203 PMC Full Text View journal details
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