title: Molecular dynamics of the neuronal EF-hand Ca2+-sensor Caldendrin.
abstract: 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.
authors: RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Pasham Parameshwar
authors: PP
authors: Reddy
authors: RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany; Centre for Cellular and Molecular Biology, CSIR, Hyderabad, India.
authors: Vijeta
authors: V
authors: Raghuram
authors: RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Johannes
authors: J
authors: Hradsky
authors: RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Christina
authors: C
authors: Spilker
authors: Centre for Cellular and Molecular Biology, CSIR, Hyderabad, India.
authors: Asima
authors: A
authors: Chakraborty
authors: Centre for Cellular and Molecular Biology, CSIR, Hyderabad, India.
authors: Yogendra
authors: Y
authors: Sharma
authors: RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany; Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Marina
authors: M
authors: Mikhaylova
authors: RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Michael R
authors: MR
authors: Kreutz
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D020832:EF Hand Motifs / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D056004:Molecular Dynamics Simulation; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002135:Calcium-Binding Proteins; D020033:Protein Isoforms; C085577:Ca2+-binding protein-1; D008274:Magnesium; D002118:Calcium