Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: structural insights into MKP-3 activation by ERK2
| Autor: | A, Farooq, G, Chaturvedi, S, Mujtaba, O, Plotnikova, L, Zeng, C, Dhalluin, R, Ashton, M M, Zhou |
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| Rok vydání: | 2001 |
| Předmět: |
Mitogen-Activated Protein Kinase 1
Models Molecular Binding Sites Recombinant Fusion Proteins Blotting Western Molecular Sequence Data Static Electricity Models Biological Protein Structure Secondary Protein Structure Tertiary Enzyme Activation Dual Specificity Phosphatase 6 Mutagenesis Catalytic Domain Humans Amino Acid Sequence Protein Tyrosine Phosphatases Nuclear Magnetic Resonance Biomolecular Sequence Alignment Protein Binding |
| Zdroj: | Molecular cell. 7(2) |
| ISSN: | 1097-2765 |
| Popis: | MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3. |
| Databáze: | OpenAIRE |
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