Molecular dynamics of the neuronal EF-hand CA2+-sensor Caldendrin
| Autor: | Reddy, P.P., Raghuram, V., Hradsky, J., Spilker, C., Shakrabory, A., Sharma, Y., Mikhaylova, Marina, Kreutz, M.R., Sub Cell Biology, Celbiologie |
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| Přispěvatelé: | Sub Cell Biology, Celbiologie |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Yellow fluorescent protein
Protein Folding Conformational change Protein Conformation lcsh:Medicine Plasma protein binding Biochemistry Rats Sprague-Dawley Mice 0302 clinical medicine Protein structure Protein Isoforms Magnesium lcsh:Science Cells Cultured Neurons Genetics 0303 health sciences Multidisciplinary EF hand Neurochemistry Recombinant Proteins Protein folding Protein Binding Research Article Signal Transduction Protein Structure Molecular Dynamics Simulation Biology 03 medical and health sciences Calcium-Mediated Signal Transduction Animals Humans EF Hand Motifs 030304 developmental biology lcsh:R Calcium-Binding Proteins Biology and Life Sciences Proteins Cell Biology Protein tertiary structure Protein Structure Tertiary Rats HEK293 Cells Förster resonance energy transfer Biophysics biology.protein lcsh:Q Calcium 030217 neurology & neurosurgery |
| Zdroj: | PLoS One, 9(7). Public Library of Science PLoS ONE PLoS ONE, Vol 9, Iss 7, p e103186 (2014) |
| ISSN: | 1932-6203 |
| Popis: | Caldendrin, L- and S-CaBP1 are CaM-like Ca2+-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 Ca2+-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 Ca2+ and Mg2+ with a global Kd in the low µM range. Interestingly, the Mg2+-binding affinity is clearly higher than in S-CaBP1, suggesting that the extended N-terminus might influence Mg2+-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 Ca2+-binding to Mg2+-saturated protein. Complex inter- and intramolecular interactions that are regulated by Ca2+-binding, high Mg2+- and low Ca2+-binding affinity, a rigid first EF-hand domain and little conformational change upon titration with Ca2+ of Mg2+-liganted protein suggest different modes of binding to target interactions as compared to classical neuronal Ca2+-sensors. |
| Databáze: | OpenAIRE |
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