Molecular plasticity of β-catenin: New insights from single-molecule measurements and MD simulation
| Autor: | Michael A. Horton, Monica Ritco-Vonsovici, Abdessamad Ababou |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Protein Conformation Surface Properties Cellular differentiation Molecular Sequence Data Static Electricity Enzyme-Linked Immunosorbent Assay Ligands Biochemistry Protein Structure Secondary Article Molecular dynamics Molecule Computer Simulation Histidine Amino Acid Sequence Binding site Fluorescent Antibody Technique Indirect Molecular Biology Horseradish Peroxidase beta Catenin Glutathione Transferase Binding Sites Sequence Homology Amino Acid Chemistry Wnt signaling pathway Force spectroscopy Affinities Cell biology Catenin Aluminum Silicates TCF Transcription Factors Transcription Factor 7-Like 2 Protein Protein Binding |
| Zdroj: | Protein Science. 16:1984-1998 |
| ISSN: | 1469-896X 0961-8368 |
| DOI: | 10.1110/ps.072773007 |
| Popis: | The multifunctional protein, beta-catenin, has essential roles in cell adhesion and, through the Wnt signaling pathway, in controlling cell differentiation, development, and generation of cancer. Could distinct molecular forms of beta-catenin underlie these two functions? Our single-molecule force spectroscopy of armadillo beta-catenin, with molecular dynamics (MD) simulation, suggests a model in which the cell generates various forms of beta-catenin, in equilibrium. We find beta-catenin and the transcriptional factor Tcf4 form two complexes with different affinities. Specific cellular response is achieved by the ligand binding to a particular matching preexisting conformer. Our MD simulation indicates that complexes derive from two conformers of the core region of the protein, whose preexisting molecular forms could arise from small variations in flexible regions of the beta-catenin main binding site. This mechanism for the generation of the various forms offers a route to tailoring future therapeutic strategies. |
| Databáze: | OpenAIRE |
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