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Molecular Dynamics of the Neuronal EF-Hand Ca(2+)-Sensor Caldendrin
Caldendrin, L- and S-CaBP1 are CaM-like Ca(2+)-sensors with different N-termini that arise from alternative splicing of the Caldendrin/CaBP1 gene and that appear to play an important role in neuronal Ca(2+)-signaling. In this paper we show that Caldendrin is abundantly present in brain while the sho...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110014/ https://www.ncbi.nlm.nih.gov/pubmed/25058677 http://dx.doi.org/10.1371/journal.pone.0103186 |
Sumario: | Caldendrin, L- and S-CaBP1 are CaM-like Ca(2+)-sensors with different N-termini that arise from alternative splicing of the Caldendrin/CaBP1 gene and that appear to play an important role in neuronal Ca(2+)-signaling. In this paper we show that Caldendrin is abundantly present in brain while the shorter splice isoforms L- and S-CaBP1 are not detectable at the protein level. Caldendrin binds both Ca(2+) and Mg(2+) with a global K(d) in the low µM range. Interestingly, the Mg(2+)-binding affinity is clearly higher than in S-CaBP1, suggesting that the extended N-terminus might influence Mg(2+)-binding of the first EF-hand. Further evidence for intra- and intermolecular interactions of Caldendrin came from gel-filtration, surface plasmon resonance, dynamic light scattering and FRET assays. Surprisingly, Caldendrin exhibits very little change in surface hydrophobicity and secondary as well as tertiary structure upon Ca(2+)-binding to Mg(2+)-saturated protein. Complex inter- and intramolecular interactions that are regulated by Ca(2+)-binding, high Mg(2+)- and low Ca(2+)-binding affinity, a rigid first EF-hand domain and little conformational change upon titration with Ca(2+) of Mg(2+)-liganted protein suggest different modes of binding to target interactions as compared to classical neuronal Ca(2+)-sensors. |
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