Structural Insights into Ca2+-dependent Regulation of Inositol 1,4,5-Trisphosphate Receptors by CaBP1
| Autor: | Katsuhiko Mikoshiba, Franciose Haeseleer, James B. Ames, Mitsuhiko Ikura, Congmin Li, Jenny Chan, Krzysztof Palczewski |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Calmodulin Molecular Sequence Data Sequence alignment Biology Biochemistry chemistry.chemical_compound Cytosol Calcium-binding protein Humans Inositol 1 4 5-Trisphosphate Receptors Magnesium Inositol Amino Acid Sequence EF Hand Motifs Protein Structure Quaternary Receptor Nuclear Magnetic Resonance Biomolecular Molecular Biology Peptide sequence Calcium-Binding Proteins Mechanisms of Signal Transduction Isothermal titration calorimetry Cell Biology Protein Structure Tertiary Crystallography chemistry Biophysics biology.protein Calcium Protein Multimerization Sequence Alignment |
| Zdroj: | Journal of Biological Chemistry. 284:2472-2481 |
| ISSN: | 0021-9258 |
| Popis: | Calcium-binding protein 1 (CaBP1), a neuron-specific member of the calmodulin (CaM) superfamily, modulates Ca2+-dependent activity of inositol 1,4,5-trisphosphate receptors (InsP3Rs). Here we present NMR structures of CaBP1 in both Mg2+-bound and Ca2+-bound states and their structural interaction with InsP3Rs. CaBP1 contains four EF-hands in two separate domains. The N-domain consists of EF1 and EF2 in a closed conformation with Mg2+ bound at EF1. The C-domain binds Ca2+ at EF3 and EF4, and exhibits a Ca2+-induced closed to open transition like that of CaM. The Ca2+-bound C-domain contains exposed hydrophobic residues (Leu132, His134, Ile141, Ile144, and Val148) that may account for selective binding to InsP3Rs. Isothermal titration calorimetry analysis reveals a Ca2+-induced binding of the CaBP1 C-domain to the N-terminal region of InsP3R (residues 1-587), whereas CaM and the CaBP1 N-domain did not show appreciable binding. CaBP1 binding to InsP3Rs requires both the suppressor and ligand-binding core domains, but has no effect on InsP3 binding to the receptor. We propose that CaBP1 may regulate Ca2+-dependent activity of InsP3Rs by promoting structural contacts between the suppressor and core domains. |
| Databáze: | OpenAIRE |
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