Tumor-Suppressor p53TAD
| Autor: | Erika F, Dudás, Gyula, Pálfy, Dóra K, Menyhárd, Fanni, Sebák, Péter, Ecsédi, László, Nyitray, Andrea, Bodor |
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| Rok vydání: | 2020 |
| Předmět: |
p53
NMR structures Full Paper Protein Conformation fuzzy complexes molecular dynamics simulations Molecular Dynamics Simulation Full Papers protein folding Humans S100A4 S100 Calcium-Binding Protein A4 Tumor Suppressor Protein p53 Hydrophobic and Hydrophilic Interactions Nuclear Magnetic Resonance Biomolecular |
| Zdroj: | Chembiochem |
| ISSN: | 1439-7633 |
| Popis: | Conformationally flexible protein complexes represent a major challenge for structural and dynamical studies. We present herein a method based on a hybrid NMR/MD approach to characterize the complex formed between the disordered p53TAD1–60 and the metastasis‐associated S100A4. Disorder‐to‐order transitions of both TAD1 and TAD2 subdomains upon interaction is detected. Still, p53TAD1–60 remains highly flexible in the bound form, with residues L26, M40, and W53 being anchored to identical hydrophobic pockets of the S100A4 monomer chains. In the resulting “fuzzy” complex, the clamp‐like binding of p53TAD1–60 relies on specific hydrophobic anchors and on the existence of extended flexible segments. Our results demonstrate that structural and dynamical NMR parameters (cumulative Δδ, SSP, temperature coefficients, relaxation time, hetNOE) combined with MD simulations can be used to build a structural model even if, due to high flexibility, the classical solution structure calculation is not possible. Fuzzy in focus: The presented hybrid NMR/MD approach indicates the disorder‐to‐order transition of p53TAD1–60 upon interaction with S100A4. p53TAD1–60 remains highly flexible, forms a clamp‐like “fuzzy” complex with three helical regions, and residues L26, M40, W53 are anchored to S100A4. |
| Databáze: | OpenAIRE |
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