Chataigner, L;
Guo, J;
Erskine, PT;
Coker, AR;
Wood, SP;
Gombos, Z;
Cooper, JB;
(2016)
Binding of Gd3+ to the neuronal signalling protein calexcitin identifies an exchangeable Ca2+-binding site.
Acta Crystallographica Section F: Structural Biology and Crystallization Communications
, F72
(4)
pp. 276-281.
10.1107/S2053230X16003526.
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Abstract
Calexcitin was first identified in the marine snail Hermissenda crassicornis as a neuronal-specific protein that becomes upregulated and phosphorylated in associative learning. Calexcitin possesses four EF-hand motifs, but only the first three (EF-1 to EF-3) are involved in binding metal ions. Past work has indicated that under physiological conditions EF-1 and EF-2 bind Mg2+ and Ca2+, while EF-3 is likely to bind only Ca2+. The fourth EF-hand is nonfunctional owing to a lack of key metal-binding residues. The aim of this study was to use a crystallographic approach to determine which of the three metal-binding sites of calexcitin is most readily replaced by exogenous metal ions, potentially shedding light on which of the EF-hands play a `sensory' role in neuronal calcium signalling. By co-crystallizing recombinant calexcitin with equimolar Gd3+ in the presence of trace Ca2+, EF-1 was shown to become fully occupied by Gd3+ ions, while the other two sites remain fully occupied by Ca2+. The structure of the Gd3+-calexcitin complex has been refined to an R factor of 21.5% and an Rfree of 30.4% at 2.2 Å resolution. These findings suggest that EF-1 of calexcitin is the Ca2+-binding site with the lowest selectivity for Ca2+, and the implications of this finding for calcium sensing in neuronal signalling pathways are discussed.
Type: | Article |
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Title: | Binding of Gd3+ to the neuronal signalling protein calexcitin identifies an exchangeable Ca2+-binding site |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1107/S2053230X16003526 |
Publisher version: | http://doi.org/10.1107/S2053230X16003526 |
Language: | English |
Additional information: | © 2016 International Union of Crystallography |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemical Research Methods, Biochemistry & Molecular Biology, Biophysics, Crystallography, neuronal calcium signalling, EF-hand, protein structure, heavy-atom complex, co-crystallization, STRUCTURE VALIDATION, DATA QUALITY, KINASE-C, X-RAY, HERMISSENDA, CALCIUM, MEMORY, CRYSTALLIZATION, MODEL, PHOTORECEPTOR |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
URI: | https://discovery.ucl.ac.uk/id/eprint/1481520 |
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